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DHVI.DUKE.EDUPublished April 2024

OUR MISSIONThe Duke Human Vaccine Institute (DHVI) will develop vaccines and therapeuticsagainst diseases of global importance while training the next generation of scientists.OUR VALUESDHVI supports the development of vaccines and therapeutics through a commitmentto Innovation, Collaboration, and Excellence.CONTENTS Research Triangle Park CampusMessage from the Director and COO,DHVI Expansion35Information for Our Community, TopAchievements, Highlighted PublicationsLeadershipAreas of Focus1011HIV Immune Response Assessment andQuality Programs121416171913Diversity, Equity, and InclusionTraining and Mentoring ProgramWhere We Are HeadedGifts of Support2930313221Center for Innovative HIV/AIDS Vaccineand Cure ResearchPancoronavirus Vaccine DevelopmentStructural BiologyInfluenza Vaccine Development DHVI Product DevelopmentPreclinical and Translational VaccineDevelopment for HIV and OtherCandidate AgentsCover photo: DHVI Medical Sciences Research Building II 15HIV Vaccine Development222325DHVI Clinical Trials UnitPandemic PreparednessDuke Regional Biocontainment Laboratory27Quantitative Research Division28Cancer Immunotherapy24DARPA

The Duke Human Vaccine Institute (DHVI) is a collaborative and multidisciplinary organization thatallows our research teams to address complex scientific questions rapidly. Thus, DHVI carries out arobust iterative vaccine development program capable of successfully tackling major globalinfectious diseases such as COVID-19, HIV, and influenza. We are fortunate to have anexperienced, cutting-edge administrative management team at DHVI bringing extensive financialand sponsored research management, project management and compliance support to faculty.DHVI has developed best practices for the administration of large research programs for makingvaccines and therapeutic antibodies against HIV, influenza, and emerging coronaviruses. Inaddition, DHVI stands ready to respond to any new emerging infectious disease threat.While the world was shutting down in 2020-2021, DHVI faculty, staff, and administrators workedtirelessly to support COVID-19 testing, next generation vaccines, and therapeutic antibodydevelopment efforts. During this time, we also expanded our campus to an additional site atResearch Triangle Park, supporting not only our translational science and clinical programs, butalso our vaccine product development team. Pivotal to the support of the Duke community duringthe pandemic, DHVI developed a COVID-19 testing program to support surveillance testing to keepDuke University open. At the height of testing, the DHVI testing team performed 35,000 tests perweek with a turnaround time of less than 24 hours.DHVI is now using what we have learned during the SARS-CoV-2 and HIV-1 pandemics and istranslating that knowledge and vaccine development know-how to establish rapid-responseplatforms for mRNA and protein vaccines. DHVI has a pipeline in place with the goal of sequencingany new pathogens and being able to rapidly develop a vaccine or therapeutic antibody.DHVI faculty and staff are dedicated to solving the global HIV crisis through development of an HIVvaccine and lead a large consortium that aims to develop a universal influenza vaccine. DHVI ismaking progress on these and other vaccines and we hope the information you find in this reportwill be of interest and helpful as you learn more about the role of vaccines in protecting societyfrom existing and new infectious disease threats.DIRECTOR BARTON HAYNES, MDCHIEF OPERATING OFFICER THOMAS DENNY, MSC, MPHIL3

In 2017 and 2018, the Duke Human Vaccine Institute experienced a rapid period of growth due toexpansion of the HIV vaccine program and initiation of the Collaborative Influenza VaccineInnovation Centers (CIVICs). With the increase in manufacturing needs and Phase 1 clinical trials inhumans, Duke expanded DHVI’s footprint and several DHVI teams have moved to the Parmer RTPresearch and development campus, ten minutes from Duke’s main campus. Thomas Denny, MSc,MPhil, chief operating officer of DHVI, is the associate dean for RTP and oversees all operations atthe new site for DHVI and the Duke School of Medicine.4Expansion of DHVI to a Second Campusin Research Triangle Park (RTP)Included in this move:DHVI Sample Repository and Accessioning Unit led by Anthony Moody that houses over onemillion human or animal cell tissue samples,Duke Vaccine and Trials Unit led by Emmanuel Walter,CIVICs influenza vaccine program led by Anthony Moody, andIVQAC program led by Denny.In addition, DHVI members Nick Heaton, Georgia Tomaras, and Garnett Kelsoe moved theirlaboratories to RTP in 2022. In the fall of 2024, DHVI members Guido Ferrari and Justin Pollara alsomove their laboratories to newly renovated RTP spaces along with the process development group,part of DHVI’s GMP team. The RTP campus supports ongoing and rapidly evolving vaccinedevelopment research where investigators lead programs to develop new influenza vaccines as wellas clinical trials to test new influenza and universal COVID-19 vaccines.Denny Lab at RTP CampusJerry Peters, lab research analyst, loads quality controlmaterial to prepare the Abbott Alinity m analyzer for HIV-1Viral Load Testing. Research Triangle Park Campus

DHVI’s efforts to combat the COVID-19pandemic are featured in a WRAL-TVdocumentary. Scientists at the Duke Human Vaccine Institute provided vital informationthroughout the COVID-19 pandemic, reaching the public through features andinterviews in broadcast, print, and online articles.The Raleigh News and Observer newspaper interviewed Kevin Saunders,PhD, on developing vaccines and mentoring young scientists.Phase 1 clinical trial launched, testing thesafety of a vaccine candidate developedunder DHVI’s CIVICs program.PBS’s Sci NC program featured Barton Haynes,MD, and Kevin Saunders, PhD, explaining thework that goes into creating a vaccine that mayprotect against all potential coronaviruses. CNN’s Sanjay Gupta interviewed Saunders onhow a universal vaccine could be the future ofthe coronavirus fight.5INFORMATION FOR OUR COMMUNITY

DHVI investigators received the International BIAL Award forVaccine Technology for their paper published in Nature in 2017on successful development of an mRNA-based ZIKA vaccine. With Drew Weissman, 2023 Nobel laureate, the team’s studyfirst demonstrated the effectiveness of modified mRNA-basedtechnology for use as a vaccine, technology that is now used in the Pfizer-BioNTech and Moderna vaccines to prevent COVID-19.DHVI was chosen to serve as the NationalCoordinating Center for surveillance of influenza,COVID-19 and respiratory viruses, supporting theCDC and a network of seven study sites as part ofthe U.S. Flu Vaccine Effectiveness network. Thenetwork is designed to measure how well a vaccineworks in the real world.Duke Human Vaccine Institute received the Duke Presidential Award thatrecognized DHVI scientists and staff who responded to the pandemic bydeveloping anti-COVID-19 antibodies and new vaccines for resistant variants ofSARS-CoV-2.The Immunology Quality Assessment (IQA) program was renewed through 2028. TheNational Institute of Allergy and Infectious Diseases (NIAID) funds the IQA program,providing quality controls and monitoring for all NIAID grants and contracts.DHVI received an NIAID contract to manufacture the next-generation coronavirusvaccine, protecting against multiple types of coronavirus and SARS-CoV-2 variants. The Duke Human Vaccine Institute's investigators have made significantscientific breakthroughs, earning multiple sponsored awards.6U.S. Flu Vaccine Effectiveness networkTOP ACHIEVEMENTS

7HIGHLIGHTEDPUBLICATIONS2022Walter EB, Talaat KR, Sabharwal C, Gurtman A, Lockhart S, Paulsen GC, Barnett ED, Muñoz FM, Maldonado Y,Pahud BA, Domachowske JB, Simões EAF, Sarwar UN, Kitchin N, Cunliffe L, Rojo P, Kuchar E, Rämet M, MunjalI, Perez JL, Frenck RW Jr, Lagkadinou E, Swanson KA, Ma H, Xu X, Koury K, Mather S, Belanger TJ, Cooper D,Türeci Ö, Dormitzer PR, Şahin U, Jansen KU, Gruber WC; C4591007 Clinical Trial Group. Evaluation of theBNT162b2 COVID-19 Vaccine in Children 5 to 11 Years of Age. N Engl J Med. 2022 Jan 6;386(1):35-46. doi:10.1056/NEJMoa2116298. PMID: 34752019Martinez DR, Schäfer A, Gobeil S, Li D, De la Cruz G, Parks R, Lu X, Barr M, Stalls V, Janowska K, Beaudoin E,Manne K, Mansouri K, Edwards RJ, Cronin K, Yount B, Anasti K, Montgomery SA, Tang J, Golding H, Shen S,Zhou T, Kwong PD, Graham BS, Mascola JR, Montefiori DC, Alam SM, Sempowski G, Sempowski GD, KhuranaS, Wiehe K, Saunders KO, Acharya P, Haynes BF, Baric RS. A broadly cross-reactive antibody neutralizes andprotects against sarbecovirus challenge in mice. Sci Transl Med. 2022 Jan 26;14(629):eabj7125. doi:10.1126/scitranslmed.abj7125. PMID: 34726473Li D, Sempowski GD, Saunders KO, Acharya P, Haynes BF. SARS-CoV-2 Neutralizing Antibodies for COVID-19Prevention and Treatment. Annu Rev Med. 2022 Jan 27;73:1-16. doi: 10.1146/annurev-med-042420-113838.PMID: 34428080Mu Z, Wiehe K, Saunders KO, Henderson R, Cain DW, Parks R, Martik D, Mansouri K, Edwards RJ, Newman A,Lu X, Xia SM, Eaton A, Bonsignori M, Montefiori D, Han Q, Venkatayogi S, Evangelous T, Wang Y, Rountree W,Korber B, Wagh K, Tam Y, Barbosa C, Alam SM, Williams WB, Tian M, Alt FW, Pardi N, Weissman D, Haynes BF.mRNA-encoded HIV-1 Env trimer ferritin nanoparticles induce monoclonal antibodies that neutralizeheterologous HIV-1 isolates in mice. Cell Rep. 2022 Mar 15;38(11):110514. doi: 10.1016/j.celrep.2022.110514.PMID: 3529488Li D, Brackenridge S, Walters LC, Swanson O, Harlos K, Rozbesky D, Cain DW, Wiehe K, Scearce RM, Barr M,Mu Z, Parks R, Quastel M, Edwards RJ, Wang Y, Rountree W, Saunders KO, Ferrari G, Borrow P, Jones EY, AlamSM, Azoitei ML, Gillespie GM, McMichael AJ, Haynes BF. Mouse and human antibodies bind HLA-E-leaderpeptide complexes and enhance NK cell cytotoxicity. Commun Biol. 2022 Mar 28;5(1):271. doi:10.1038/s42003-022-03183-5. PMID: 35347236Whitley J, Zwolinski C, Denis C, Maughan M, Hayles L, Clarke D, Snare M, Liao H, Chiou S, Marmura T, ZoellerH, Hudson B, Peart J, Johnson M, Karlsson A, Wang Y, Nagle C, Harris C, Tonkin D, Fraser S, Capiz L, Zeno CL,Meli Y, Martik D, Ozaki DA, Caparoni A, Dickens JE, Weissman D, Saunders KO, Haynes BF, Sempowski GD,Denny TN, Johnson MR. Development of mRNA manufacturing for vaccines and therapeutics: mRNA platformrequirements and development of a scalable production process to support early phase clinical trials. TranslRes. 2022 Apr;242:38-55. doi: 10.1016/j.trsl.2021.11.009. PMID: 34871810

8Gobeil SM, Henderson R, Stalls V, Janowska K, Huang X, May A, Speakman M, Beaudoin E, Manne K, Li D,Parks R, Barr M, Deyton M, Martin M, Mansouri K, Edwards RJ, Eaton A, Montefiori DC, Sempowski GD,Saunders KO, Wiehe K, Williams W, Korber B, Haynes BF, Acharya P. Structural diversity of the SARS-CoV-2Omicron spike. Mol Cell. 2022 Jun 2;82(11):2050-2068.e6. doi: 10.1016/j.molcel.2022.03.028. PMID: 35447081Stalls V, Lindenberger J, Gobeil SM, Henderson R, Parks R, Barr M, Deyton M, Martin M, Janowska K, Huang X,May A, Speakman M, Beaudoin E, Kraft B, Lu X, Edwards RJ, Eaton A, Montefiori DC, Williams WB, SaundersKO, Wiehe K, Haynes BF, Acharya P. Cryo-EM structures of SARS-CoV-2 Omicron BA.2 spike. Cell Rep. 2022Jun 28;39(13):111009. doi: 10.1016/j.celrep.2022.111009. PMID: 35732171Saunders KO, Edwards RJ, Tilahun K, Manne K, Lu X, Cain DW, Wiehe K, Williams WB, Mansouri K, HernandezGE, Sutherland L, Scearce R, Parks R, Barr M, DeMarco T, Eater CM, Eaton A, Morton G, Mildenberg B, Wang Y,Rountree RW, Tomai MA, Fox CB, Moody MA, Alam SM, Santra S, Lewis MG, Denny TN, Shaw GM, MontefioriDC, Acharya P, Haynes BF. Stabilized HIV-1 envelope immunization induces neutralizing antibodies to theCD4bs and protects macaques against mucosal infection. Sci Transl Med. 2022 Sep 7;14(661):eabo5598. doi:10.1126/scitranslmed.abo5598. PMID: 36070369Li D, Martinez DR, Schäfer A, Chen H, Barr M, Sutherland LL, Lee E, Parks R, Mielke D, Edwards W, Newman A,Bock KW, Minai M, Nagata BM, Gagne M, Douek DC, DeMarco CT, Denny TN, Oguin TH 3rd, Brown A, RountreeW, Wang Y, Mansouri K, Edwards RJ, Ferrari G, Sempowski GD, Eaton A, Tang J, Cain DW, Santra S, Pardi N,Weissman D, Tomai MA, Fox CB, Moore IN, Andersen H, Lewis MG, Golding H, Seder R, Khurana S, Baric RS,Montefiori DC, Saunders KO, Haynes BF. Breadth of SARS-CoV-2 neutralization and protection induced by ananoparticle vaccine. Nat Commun. 2022 Oct 23;13(1):6309. doi: 10.1038/s41467-022-33985-4. PMID:36274085Luo S, Zhang J, Kreutzberger AJB, Eaton A, Edwards RJ, Jing C, Dai HQ, Sempowski GD, Cronin K, Parks R, YeAY, Mansouri K, Barr M, Pishesha N, Williams AC, Vieira Francisco L, Saminathan A, Peng H, Batra H, Bellusci L,Khurana S, Alam SM, Montefiori DC, Saunders KO, Tian M, Ploegh H, Kirchhausen T, Chen B, Haynes BF, AltFW. An antibody from single human VH-rearranging mouse neutralizes all SARS-CoV-2 variants through BA.5by inhibiting membrane fusion. Sci Immunol. 2022 Oct 28;7(76):eadd5446. doi: 10.1126/sciimmunol.add5446.PMID: 359517672023Wrapp D, Mu Z, Thakur B, Janowska K, Ajayi O, Barr M, Parks R, Mansouri K, Edwards RJ, Hahn BH, Acharya P,Saunders KO, Haynes BF. Structure-Based Stabilization of SOSIP Env Enhances Recombinant EctodomainDurability and Yield. J Virol. 2023 Jan 31;97(1):e0167322. doi: 10.1128/jvi.01673-22. PMID: 36633409Cohen KW, Fiore-Gartland A, Walsh SR, Yusim K, Frahm N, Elizaga ML, Maenza J, Scott H, Mayer KH, GoepfertPA, Edupuganti S, Pantaleo G, Hutter J, Morris DE, De Rosa SC, Geraghty DE, Robb ML, Michael NL, Fischer W,Giorgi EE, Malhi H, Pensiero MN, Ferrari G, Tomaras GD, Montefiori DC, Gilbert PB, McElrath MJ, Haynes BF,Korber BT, Baden LR; NIAID HVTN 106 Study Group. Trivalent mosaic or consensus HIV immunogens primehumoral and broader cellular immune responses in adults. J Clin Invest. 2023 Feb 15;133(4):e163338. doi:10.1172/JCI163338. PMID: 36787249

9Haynes BF, Wiehe K, Borrow P, Saunders KO, Korber B, Wagh K, McMichael AJ, Kelsoe G, Hahn BH, Alt F, ShawGM Strategies for HIV-1 vaccines that induce broadly neutralizing antibodies.Nat Rev Immunol. 2023 Mar;23(3):142-158. doi: 10.1038/s41577-022-00753-w. PMID: 35962033Heggestad JT, Britton RJ, Kinnamon DS, Liu J, Anderson JG, Joh DY, Quinn Z, Fontes CM, Hucknall AM, ParksR, Sempowski GD, Denny TN, Burke TW, Haynes BF, Woods CW, Chilkoti A. COVID-19 Diagnosis and SARS-CoV-2 Strain Identification by a Rapid, Multiplexed, Point-of-Care Antibody Microarray. Anal Chem. 2023 Apr4;95(13):5610-5617. doi: 10.1021/acs.analchem.2c05180. Epub 2023 Mar 24. PMID: 36961989 Henderson R, Zhou Y, Stalls V, Wiehe K, Saunders KO, Wagh K, Anasti K, Barr M, Parks R, Alam SM, Korber B,Haynes BF, Bartesaghi A, Acharya P. Structural basis for breadth development in the HIV-1 V3-glycan targetingDH270 antibody clonal lineage. Nat Commun. 2023 May 15;14(1):2782. doi: 10.1038/s41467-023-38108-1.PMID: 37188681Swanson O, Martin Beem JS, Rhodes B, Wang A, Barr M, Chen H, Parks R, Saunders KO, Haynes BF, Wiehe K,Azoitei ML. Identification of CDRH3 loops in the B cell receptor repertoire that can be engaged by candidateimmunogens. PLoS Pathog. 2023 May 17;19(5):e1011401. doi: 10.1371/journal.ppat.1011401. PMID: 37196027May AJ, Pothula KR, Janowska K, Acharya P. Structures of Langya Virus Fusion Protein Ectodomain in Pre- andPostfusion Conformation. J Virol. 2023 Jun 29;97(6):e0043323. doi: 10.1128/jvi.00433-23. Epub 2023 Jun 6.PMID: 37278642; PMCID: PMC10308951.Martin Beem JS, Venkatayogi S, Haynes BF, Wiehe K. ARMADiLLO: a web server for analyzing antibodymutation probabilities. Nucleic Acids Res. 2023 Jul 5;51(W1):W51-W56. doi: 10.1093/nar/gkad398. PMID:37260077Martinez DR, Schäfer A, Gavitt TD, Mallory ML, Lee E, Catanzaro NJ, Chen H, Gully K, Scobey T, Korategere P,Brown A, Smith L, Parks R, Barr M, Newman A, Bowman C, Powers JM, Soderblom EJ, Mansouri K, Edwards RJ,Baric RS, Haynes BF, Saunders KO. Vaccine-mediated protection against Merbecovirus and Sarbecoviruschallenge in mice. Cell Rep. 2023 Oct 31;42(10):113248. doi: 10.1016/j.celrep.2023.113248. PMID: 37858337Haynes BF, Wiehe K, Alam SM, Weissman D, Saunders KO. Progress with induction of HIV broadly neutralizingantibodies in the Duke Consortia for HIV/AIDS Vaccine Development. Curr Opin HIV AIDS. 2023 Nov1;18(6):300-308. doi: 10.1097/COH.0000000000000820. Epub 2023 Sep 25. PMID: 37751363Kapingidza AB, Marston DJ, Harris C, Wrapp D, Winters K, Mielke D, Xiaozhi L, Yin Q, Foulger A, Parks R, BarrM, Newman A, Schäfer A, Eaton A, Flores JM, Harner A, Catanzaro NJ Jr, Mallory ML, Mattocks MD, Beverly C,Rhodes B, Mansouri K, Van Itallie E, Vure P, Dunn B, Keyes T, Stanfield-Oakley S, Woods CW, Petzold EA,Walter EB, Wiehe K, Edwards RJ, Montefiori DC, Ferrari G, Baric R, Cain DW, Saunders KO, Haynes BF, AzoiteiML. Engineered immunogens to elicit antibodies against conserved coronavirus epitopes. Nat Commun. 2023Nov 30;14(1):7897. doi: 10.1038/s41467-023-43638-9. PMID: 38036525

10Barton Haynes Thomas DennyDirector Chief Operating OfficerKevin SaundersAssociate DirectorEmmanuel WalterMichelle SmithChief Medical OfficerChief Administrative OfficerKelly CuttleChief of StaffMaria BlasiScott AldermanCo-Director of Duke Training& Mentoring ProgramAssociate Director of RegionalBiocontainment LaboratoryColin Duckett Co-Director of RegionalBiocontainment LaboratoryAlthaf HussainSenior Director of ProductDevelopmentAnthony MoodyWilton WilliamsDirector of Duke CIVICsVaccine CenterCo-Director of Duke Training& Mentoring ProgramKevin WieheDirector of ResearchHerman StaatsCo-Director of RegionalBiocontainment LaboratoryDHVI LEADERSHIP2022-2023

AREAS OF FOCUSDHVI faculty focus on performing the basic science needed to find the enabling technology for novel vaccineand therapeutics development. We then translate our basic science discoveries into products that can betested in in vitro and in vivo preclinical studies. When preclinical studies are successful, DHVI has its own goodmanufacturing practice (GMP) facility for producing vaccines or therapeutics as well as our own clinical trialsunit for testing these new products in human clinical trials.11The DHVI team has established two major vaccine platforms that can be used for many vaccines: messengerRNA (mRNA) and protein nanoparticles, both of which can be used for development of vaccines against manyinfectious agents.The areas of focus in DHVI include HIV-1, influenza, pancoronavirus vaccine development, sexually transmittedinfections, structural biology of virus pathogenesis and vaccine design, vaccine platform development to beprepared to respond rapidly to new epidemics, computational biology and artificial intelligence (AI), and a newprogram in cancer immunotherapy.To accomplish our missions, we also have dedicated programs in trainee mentorship and development anddiversity, inclusion, and equity. What follows are brief outlines of the ongoing work in these areas.

The Immunology Virology Quality Assessment Center (IVQAC) is funded throughseveral National Institute of Allergy and Infectious Diseases (NIAID)contracts that provide quality assurance programs and resources to domesticand international NIAID-funded investigators and their laboratories. The IVQACis led by principal investigator, Thomas Denny, MSc, MPhil, and evaluates andenhances the integrity and comparability of immunological laboratorydeterminations performed in samples collected from multi-site HIV/AIDStherapeutic, vaccine, and prevention clinical trials. The IVQAC provides supportto more than 10 external quality assurance programs and more than 250laboratories performing clinical testing.The IVQAC directs multiple quality assuranceprograms, including the External QualityAssurance Program Oversight Laboratory(EQAPOL), the Immunology Quality Assessment(IQA) program, the Non-Human Primate CoreVirology Laboratory (NHPCVL), and the VirologyQuality Assurance (VQA) program. Through theexpertise and infrastructure of these existingprograms, the IVQAC was well-positioned to leadthe SARS-CoV-2 surveillance program that wascarried out by the Denny laboratory during theCOVID-19 pandemic. The testing program allowedDuke to test the students and faculty at Duke byPCR on a weekly basis for the presence of SARS-CoV-2 infection.Jerry Peters, lab research analyst in theDenny lab, loads quality control materialto prepare the Abbott Alinity m analyzerfor HIV-1 Viral Load Testing.Denny loads Polymerase Chain Reaction (PCR) plates into thecobas 6800 instrument for HIV viral load testing. Thomas Denny, MSc, MPhil 12HIV IMMUNE RESPONSE ASSESSMENTAND QUALITY PROGRAMS

Guido Ferrari, MD, professor in surgery, and Wilton Williams, PhD, associate professor in surgery, receivedNIH funding for their co-principal investigators grant, “Center for Innovative HIV/AIDS Vaccine and CureResearch (CIAVCR).” The UM1 award builds upon the development of the team’s vaccine strategy to induceprotective immune responses in non-human primate (NHP) models by exploring innovative messengerribonucleic acid (mRNA) constructs for immunogen delivery that can elicit both protective and therapeutic Band T cell responses.The program has two main research focuses:CENTER FOR INNOVATIVE HIV/AIDSVACCINE AND CURE RESEARCHGuido Ferrari, MD13Wilton Williams, PhDThis UM1 presents an exciting opportunity to advance research toward protective and therapeutic vaccinestrategies for HIV, which have remained elusive, to leverage the latter to eradicate HIV infection. The in vivomechanistic studies will reveal the extent to which neutralizing antibody (NAb) and CD8 T cell responsescontribute to prevention and eradication of HIV-1 infection. The program will build upon an existing vaccinestrategy that can induce protective NAb responses in NHPs by exploring innovative mRNA constructs forimmunogen delivery that can elicit both NAb and CD8 T cell responses.The team is comprised of dedicated investigators with broad expertise from multiple institutions: DukeUniversity, University of Pennsylvania, University of North Carolina at Chapel Hill, Los Alamos NationalLaboratory, Harvard University, Oxford University, and BIOQUAL, Inc.The first, led by Williams and Barton Haynes, MD, focuses on vaccine-induced neutralizing antibodyprotection from HIV-1 infection.The second research focus, led by Ferrari and Michael Betts, PhD, professor of microbiology at theUniversity of Pennsylvania, centers on therapeutic vaccine regimen in association with immune modulatorsfor eradication of latent reservoir.

In 2022, DHVI’s Division of Structural Biologyled a collaborative NIH/NIAID U54 proposalthat was funded to start a new HIV StructuralBiology Center. The Duke Center for HIVStructural Biology (DCHSB) thus became thesixth NIH-funded structural biology center.The DCHSB is a global collaboration that will fill gaps in knowledge of the structure, function and immunerecognition of the HIV-1 Envelope glycoprotein (Env) by providing new insights into dynamics of HIV-1 entryand fusion with the host membrane, the Env-initiated immune activation of B cell receptors, and the role ofanti-Env antibodies in blocking viral rebound.In 2021-2022, a major focus of the Structural Biology Division was devotedto following the structural evolution of the SARS-CoV-2 spike in thebackdrop of an ongoing pandemic. The discoveries made on the structuralconsequences of the evolution of the SARS-CoV-2 spike, and the paperspublished from it, led to world-wide recognition of the Division as experts inSARS-CoV-2 spike structural biology. Simultaneously, the Division partneredwith DHVI colleagues in the Haynes and Saunders laboratories to studyantibodies isolated from convalescent individuals, research that laid thefoundation to develop a pancoronavirus vaccine.Salam SammourLab Research AnalystSTRUCTURAL BIOLOGYThe DHVI Division of Structural Biology brings under its umbrelladiverse technologies to DHVI, including X-ray crystallography, cryo-electron microscopy (cryo-EM), negative stain EM, small angle X-rayscattering, molecular dynamics, biophysics, FRET analysis, andbiochemistry, that work in concert to enhance understanding of theinteractions between viral pathogens and the human immune system.Members of this division use structural insights to inform vaccine designagainst diverse viral families, including HIV-1, influenza, coronaviruses,and henipavirsues.Yanshun Liu, PhDSenior Lab Research Analyst14Priyamvada Acharya, PhDDirector of the Duke Center forHIV Structural Biology

The Duke Center for HIV/AIDS Vaccine Development (CHAVD), established in 2005, is funded by the NIH/NIAIDto rapidly move vaccine immunogens into iterative discovery medicine Phase 1 clinical trials. DHVI, as the hubof this international large consortium, brings fast-paced innovative basic science to feed this vaccine pipelinewhile having GMP manufacturing capabilities on site to rapidly and effectively produce products for use inclinical trials in partnership with the HIV Vaccine Trials Network (HVTN).The development of an effective HIV-1 vaccine is challenging due tothe genetic diversity of HIV-1, immune evasion mechanisms, and theability of HIV-1 to integrate into host immune cells to becomeresistant to host immunity. Due to the complexity of HIV-1, aprotective vaccine must prevent infection from HIV-1. Antibodiesthat neutralize the virus must be present at the time of infection toprevent the infection from taking place. Thus, a prime goal of HIV-1vaccine development is the induction of antibodies that broadlyprotect against diverse HIV-1 isolates, known as broadly neutralizingantibodies or bnAbs.The Duke CHAVD preclinical program feeding this HIV-1 vaccine pipeline is innovative and robust. The DukeCHAVD is dissecting HIV-host biology to develop HIV-1 vaccine candidates. With the understanding of how Bcells make bnAbs against HIV, a goal of the Duke CHAVD program is to use vaccination to guide the immunesystem to make bnAbs - an approach called B cell lineage design. B cell lineage vaccines are being designed toinclude a sequence of immunizations that step-wise drives antibodies to develop into bnAbs.15HIV VACCINE DEVELOPMENT Mature HIV-1 virionBarton Haynes, MD, has ledthe consortia since 2005.Recent successes in Phase 1 clinical trials continue to have a major impact on the further design anddevelopment of HIV vaccines aimed at inducing bnAbs. A portfolio of immunogens, as both primes and boosts,aimed at inducing different HIV bnAb lineages now exists, and numerous HVTN Phase 1 clinical trials areongoing or in development. Therefore, the Duke CHAVD successfully continues to perform iterativeimmunogen design and development and is accelerating HIV vaccine immunogen down-selection andmanufacturing to design a prototype HIV vaccine by 2026.

In 2021, the National Institute of Allergy and InfectiousDiseases (NIAID) awarded $17.5 million over three yearsto Kevin Saunders, PhD, and the Duke Human VaccineInstitute to develop a vaccine that protects againstmultiple types of coronaviruses and viral variants thatmight emerge to infect humans in the future. The significanceof this grant is that it will provide the manufacturing platform and rationale for universal coronavirus vaccinesfor future epidemics. Such a vaccine can be immediately available at the onset of a new coronavirus epidemic,avoiding much of the human tragedy and social disruption caused by a pandemic.Model of the synthetic first generationpancoronavirus vaccine with 24 piecesof the coronavirus receptor bindingdomain (RBD) of the outer coat protein(Spike) arrayed on a bacterial protein toform a virus-like nanoparticle.When the COVID-19 pandemic began in 2020, Barton Haynes, MD,realizing that SARS-CoV-2 would rapidly mutate, quicky initiatedefforts to develop next generation vaccines against SARS-CoV-2and any new variants that might emerge. Haynes and DHVI received$17 million from the federal CARES Act through the North CarolinaLegislature to work on new coronavirus vaccines, new antibodycountermeasures and new tests for diagnosis. With this support,DHVI investigators, led by Saunders and Haynes, have developed afirst-generation pancoronavirus vaccine that was published inNature in 2021. Saunders has been awarded a manufacturingcontract from the NIAID for producing the vaccine for a Phase Iclinical trial. This vaccine neutralizes all SARS-CoV-2 variantsthrough XBB1.5.Acharya continues to study the new SARS-CoV-2 variants as theyemerge to understand how they are able to evade the body’s immunesystem even if antibodies are present from the COVID-19 vaccine.Priyamvada Acharya, PhDPriyamvada Acharya, PhD, and her team studied the protein structureson the surface of SARS-CoV-2, eventually discovering the mechanismsof virus spike protein evolution that made the virus more transmissible.In August 2021, Acharya and her team published the first of severalimportant studies in Science. The discoveries made on the structuralconsequences of the evolution of the SARS-CoV-2 spike, and the paperspublished from it, led to world-wide recognition of DHVI’s structuralbiology team led by Acharya as experts in SARS-CoV-2 spike structuralbiology.Unraveling the Mysteries of Coronavirus Interactions with the Immune SystemPANCORONAVIRUSVACCINE DEVELOPMENTKevin Saunders, PhD, associate director ofDHVI, and Barton Haynes, MD, director ofDHVI, collaborate in the Haynes lab.Protection Against Future Variants: Developing Pancoronavirus VaccinesSaunders and the DHVI team have gone on to develop a second-generation pancoronavirus vaccine that nowneutralizes not only SARS related coronaviruses but also neutralizes some of the Middle Eastern RespiratoryVirus (MERS) type of coronaviruses. The first-generation vaccine will be available for a clinical trial in humans inthe summer of 2024.16

The DHVI was awarded three separate federal contracts from the NIAID in2019 as part of a massive national effort to either develop improvedseasonal influenza vaccines or produce a universal influenza vaccine.CIVICs is comprised of three Vaccine Centers, a Manufacturing andToxicology Core, and two Clinical Cores. The CIVICs Program is acornerstone of the NIH's Universal Influenza Vaccine Strategic Plan andoffers a pathway for academic researchers to bring innovative vaccineideas from bench to bedside through this mechanism.The goal of CIVICs, led by DHVI member Anthony Moody, MD, is toimprove seasonal influenza vaccines to provide better protection againstinfection and design influenza vaccines that protect for more than oneinfluenza season and that are effective for all age groups.Now in the fourth year of the contract, CIVICs continues to expand its network of collaborative investigatorsacross the country, including academic and industry partners, to develop new vaccine platform and antigendesigns. Nine other vaccine candidates are currently in preclinical testing.The Collaborative Influenza Vaccine Innovation Centers (CIVICs)program is focused on developing both improved seasonal and universalinfluenza vaccines. Current seasonal influenza vaccines are limited indurability and their ability to protect against all influenza typescirculating in humans.INFLUENZA VACCINE DEVELOPMENTIn 2022-2023, the CIVICs team tested additional novel seasonal and universal influenza vaccines in animalmodels to identify additional candidates to move forward. The team also tests new technologies to providefaster, cheaper, and/or improved means of generating novel influenza vaccines than the current egg-basedseasonal influenza vaccine production model.The CIVICs program is comprised of three programs: the clinical core, the manufacturing and toxicology core,and the vaccine development core.CIVICs brings together a multidisciplinary team of researchers at Duke and external collaborators who areexperts in influenza biology, immunology, and vaccine development. CIVICs has moved two vaccine candidatesinto phase 1 clinical trials in collaboration with the Duke Manufacturing and Toxicology Core and the DukeCIVICs Clinical Core. CIVICs is using multiple approaches to design a broadly protective vaccine, includinghighly multivalent vaccines (Nicholas Heaton at Duke, Scott Hensley at UPenn), novel protein designs (AaronSchmidt at Ragon Institute, Kevin McCarthy at Pitt), novel inactivation technologies (Ian Ammana at NajítTechnologies), novel T-cell based approaches (Arthur Young at InvVax), new mRNA vaccine approaches (DrewWeissman at UPenn), new DNA vaccine approaches (Fan Yuan at Duke), and new approaches to enhancevaccine responses with novel adjuvants (Herman Staats at Duke).Anthony Moody, MDDirector of Duke CIVICsVaccine Center 17

The Duke CIVICs Clinical Core, under theleadership of Emmanuel Walter, MD,MPH, designs and conducts Phase I,Phase I/II, and controlled humaninfection trials to evaluate novelinfluenza vaccines. The Clinical Coreserves as the primary biorepository forthe CIVICs program which includestracking and management ofbiospecimens obtained from participantsenrolled in CIVICs clinical trials. ClinicalCore laboratories also standardize andharmonize assays used to measure theimmune responses to the vaccinestested in the CIVICs studies.Emmanuel Walter, MD, MPH, chief medical officer of DHVI,simulates counseling a clinic patient, while Lynn Harrington, RN,research practice manager, recreates preparing to administer a trialvaccine.The CIVICs Duke Manufacturing and Toxicology Core, led by ThomasDenny, MSc, MPhil, is housed within the DHVI manufacturing facility, whichfollows current good manufacturing practices (cGMP) to ensure patientsafety and product quality. The Manufacturing and Toxicology Core’s GMPprogram is designed to meet the demand for fast, iterative, early-phaseprocess development and clinical manufacturing as an enabler for researchorganizations.The Core uses flexible, non-fixed equipment to enable rapid layoutconfiguration changes that keep pace with the shifting needs of themanufacturing facility. Additionally, the team uses single-use, closedsystem unit operations in manufacturing. The GMP team includes expertsin the field with extensive experience in industry before joining DHVI,works collaboratively with third party entities routinely for toxicologystudies, and has its own regulatory staff who can prepare and submitInvestigator’s Brochures and Investigational New Drug applications. During the fourth year of the contract, the Duke CIVICs Manufacturing and Toxicology core produced andreleased its first two CIVICs vaccine candidates. Each of these vaccine candidates were designed on themRNA platform with one targeting an improved seasonal vaccine approach while the other focused on a moreuniversal vaccine approach. Moreover, Duke has been tasked to manufacture new vaccine candidates fromexternal partners and has undertaken several feasibility assessments within the network on a number ofvaccine platforms.Thomas Denny, MSc, MPhil 18

At the Duke Human Vaccine Institute, having a current Good Manufacturing Practices(cGMP) antibody and vaccine production facility makes DHVI uniquely prepared to be rapidresponders to bring antibody and vaccine countermeasures to society should a newinfectious disease epidemic arise. DHVI investigators are skilled in antibody isolation andhave two rapid response vaccine platforms into which DHVI investigators can “plug andplay” any of a number of pandemic infectious disease molecules for rapid countermeasuredevelopment. DHVI teams are positioned to speed translational efforts moving researchdiscoveries into Phase I safety clinical trials in humans by having an infrastructure to rapidlyrespond to emerging public health threats.Althaf Hussain is senior director of DHVI Product Development. A primary mission of the DHVI productdevelopment unit is to take new concepts for vaccines to clinic for evaluation in human clinical trials. Forreadiness for making novel vaccine and therapeutic antibody countermeasures for new epidemic viruses, speedis important in order to have the counter measure ready to stop an epidemic. DHVI is one of only a few placesthat can perform vaccine development from bench to bedside. This means that DHVI performs the basic andpreclinical research, makes the vaccine under GMP conditions, and then performs the Phase I clinical trial, allwithin one facility.Product Development UnitOn average, 15-18 months is standard for product development, but that’s a longtime to wait for clinical data to make the best decision on concept of a vaccine.We are working to develop protein and mRNA manufacturing platforms that willcut the manufacturing time for both proteins and mRNAs down to five to sixmonths.“We have to be compliant to FDA and other inspection agencies to be allowed todo what we do. We are a manufacturing facility in an academic institute. OurProduct Development Unit, however, performs as if it is in a biotechnologycompany.” - Althaf HussainGMP at DHVI: End-to-End Manufacturing CapabilitiesDHVI met several needs during the urgency of the COVID-19 pandemic.Pancoronavirus fill/finish production was brought on to support currentand future pandemic needs. This technology has shortened timelines toget product to clinics for trials. The DHVI GMP program successfullysupports end-to-end mRNA-LNP vaccine manufacturing capability,including fill/finish and analytical release testing. Bringing these state-of-the-art processes in-house at DHVI allows for the acceleration ofmanufacturing timelines and reduces the reliance on third parties formanufacturing and release testing. The mRNA-LNP platform capabilityenables rapid assessment of novel vaccine concepts in early phaseclinical evaluation.Since the COVID-19 pandemic,DHVI has tripled its capacity tomake products each year. DHVI PRODUCTDEVELOPMENT19Althaf HussainSenior Director of ProductDevelopment

The remarkable success of COVID-19 mRNA-based vaccines and the ensuing interest in mRNA vaccines andtherapeutics have highlighted the need for a scalable, clinical-enabling manufacturing process to produce suchproducts and robust analytical methods to demonstrate safety, potency, and purity. To address these needs,the DHVI GMP team has advanced a manufacturing process for mRNA/LNP production that is readily adaptableto GMP-compliant manufacturing and developed the required analytical methods for product characterization,quality control release, and stability testing.mRNA PlatformFill/FinishAn essential component of vaccine development and manufacturing is drug product formulation and filling intovials for clinical delivery. The GMP facility has an automated and fully enclosed fill/finish isolator designed to fillup to 1200 vials per run to enable direct drug substance to drug product production within DHVI. The fill/finishcapability enables the GMP team to formulate, fill, inspect, label, package, and release drug products forclinical trials.New fill/finish equipment fillsup to 1200 vials per lot. TheState of North Carolina, inresponse to the COVID-19pandemic, enacted the 2020COVID-19 Recovery Act. As aresult, $1.4 million wasdirected toward the equipmentto help develop a safe andeffective COVID-19 vaccinethat would be available to thepublic as soon as possible.Lipid nanoparticle encapsulation is essential to the success of mRNA vaccines and therapeutics. The lipids forma protective structure around the mRNA and deliver the payload to target cells to enable protein expressionfrom the mRNA transcript. Through our collaborations with LNP formulation partners, the DHVI GMP team hassuccessfully transferred LNP encapsulation operations into process development and GMP to enable end-to-end mRNA-LNP manufacturing capabilities.20

CERT #7043.01The Preclinical and Translational Vaccine Development for HIV and Other Candidate Agents (PTVDS)contract was awarded to Thomas Denny, MSc, MPhil, on December 1, 2021. This is an NIAID contract tosupport development of Division of AIDS (DAIDS) clinical products. The initial task order executed was tomanage part of the DAIDS clinical products inventory, and under this task order, DHVI’s team manages thestorage and shipping of materials produced under DAIDS-sponsored contracts. This work is beingperformed at two sites: the Accessioning Unit (AU) on the Duke RTP campus and SriSai BiopharmaceuticalSolutions, LLC, in Frederick, Maryland.PRECLINICAL AND TRANSLATIONALVACCINE DEVELOPMENT FOR HIV ANDOTHER CANDIDATE AGENTS DHVI was also awarded a PTVDS task order this past year to produce two HIV envelope mRNA-LNP drugproducts Phase 1 clinical trial studies in the NIAID HIV Vaccine Trials Network. The Duke team will optimizeHIV envelope sequences received from the product innovator to perform scalable in vitro transcription (IVT)reactions, followed by lipid encapsulation and purification process for the production of mRNA-LipidNanoparticles (mRNA-LNP). In addition, the team will develop and oversee analytical testing and/or assaysfor process development, manufacturing, and product release. They will also conduct short and long-termstability studies of the drug substances and drug products.DHVI ‘s Accessioning Unit is one of two storage sites in the contract for long-term storage for vaccine products/reagents from DAIDS projects.The DHVIAccessioning Unit and Biorepository recently became ISO 20387 accreditedwith the American Association of Laboratory Accreditation. It is one of only tenbiorepositories worldwide with this distinction.21

The Duke Vaccine and Trials Unit (DVTU) is DHVI’s clinical trial arm. Led by Emmanuel Walter, MD, MPH andMichael J. Smith MD, MSCE, the DVTU has three decades of experience conducting clinical investigationsrelated to the prevention, treatment, and control of infectious diseases. DVTU’s work focuses on evaluatingthe safety, immunogenicity, and effectiveness of new and existing vaccines and furthering the understandingof measures of protection from infection. Our unit serves as an NIAID funded Collaborative Influenza VaccineInnovation Centers (CIVICs) Clinical Core site, an academic site for the CDC’s Clinical Immunization SafetyAssessment Program (CISA), and a coordinating center for the CDC’s Influenza Vaccine EffectivenessNetwork. The investigative team includes clinicians across multiple disciplines encompassing pediatrics,internal medicine, geriatrics, and maternal-fetal medicine.In addition to DVTU work in the three programs noted,between 2021-2022, unit activities were heavilygeared toward the COVID-19 pandemic response. TheDVTU enrolled and followed participants in landmarktrials establishing the safety and efficacy ofPfizer/BioNTech’s mRNA COVID-19 vaccine in adultsand adolescents and AstraZeneca’s viral-vectoredCOVID-19 vaccine in adults. The DVTU then played apivotal role in the evaluation of Pfizer/ BioNTech’smRNA COVID-19 vaccine in children. With the rapidemergence of SARS-CoV-2 variants, we worked withboth federal and industry partners to evaluate thesafety and immunogenicity of booster COVID-19doses, including bivalent vaccines containing both theancestral and variant SARS-CoV-2 virus.Other recent unit investigations include a first-in-human study of an inactivated Yellow Fever Virus Vaccine, astudy of a novel RSV vaccine in infants, and a study comparing high-dose influenza vaccine to standard doseinfluenza vaccine in patients following solid organ transplant.Harringtonsimulates administering a trialvaccine at the DVTUpatient clinic.DHVI CLINICAL TRIALS UNITLynn Harrington, RN, research practicemanager, removes a trial vaccine from therefrigerator.22

The National Institute of Allergy and Infectious Disease (NIAID) launched the Centers for Research inEmerging Infectious Diseases (CREID) Network in 2020, consisting of 10 Research Centers and aCoordinating Center. The CREID Coordinating Center is co-led by Anthony Moody, MD, with the aims ofcoordinating the research and outbreak response efforts of global experts in viral pathogen transmission,vector-host lifecycle, host immunological responses, and diagnostic assay development.The CREID Network consists of 10 ResearchCenters and the Coordinating Center.CREID Coordinating Center members participate in site visits tobetter understand the capacities of CREID Network membersand where partnerships can be built.The CREID Network seeks to build collaborative partnershipswith industry, government, and local community stakeholders toidentify outbreak response strengths and needs, whileproactively aligning scientific research activities to respondquickly and efficiently to future outbreaks.The CREID Coordinating Center specific aims include:Laboratory Assay Quality,Biorepository Oversight and Quality,Data Capture and Harmonization,Capacity Building and Strengthening,Outbreak Research and Response, andPilot Program Awards, focusing heavily on mentoring thenext generation of scientists around the world.The goals of the CREID Network are to identify emerging and re-emerging pathogen outbreaks around theworld, streamline global collaboration to share reagents, technology, and samples to launch rapid responses,and build capacities of high-risk regions to respond to outbreaks faster.PANDEMIC PREPAREDNESS AT DHVIIn addition to CREID network coordination and relationship building, DHVI’s CREID Coordinating Center teamfocuses heavily on laboratory and biorepository activities. These activities include creating a virtualbiodirectory of reagents and samples for CREID Network users, optimizing lab assays developed in one labfor use in labs across the globe with regard to local resource and supply chains, creating specific kits forRUO assays, producing assay controls for distribution to Network labs during outbreak surges, and collatinglaboratory and biorepository best practices and resources. Additionally, DHVI’s Accessioning Unit is availablefor sample processing, storing, and shipment in the event of an outbreak. DHVI also works closely with thedata management experts at RTI International. Together, the CREID Coordinating Center team conductsregular webinars, discussions, training, and strategic planning to prepare for outbreaks.The CREID Research Centers, each a network of their own, consist of multidisciplinary experts in 29 countriesand across 47 research sites; the research sites include clinical, animal, and vector research activities. Theseexperts and their professional teams are currently conducting scientific research on 21 pathogen families,including: Zika, Ebola, Nipah, West Nile virus, Dengue, Japanese Encephalitis, Rift Valley Fever, MERS, YellowFever, Lassa, Coronaviruses, Chikungunya, Marburg, Crimean Congo Hemorrhagic Fever, SARS-CoV, andSARS-CoV-2. 23

The Duke Regional Biocontainment Laboratory (RBL) is part of the Defense Advanced Research ProjectsAgency (DARPA) Pandemic Prevention Platform (P3) program within the Department of Defense to addressthe challenges of rapid development of countermeasures for emerging infectious diseases. Rapiddevelopment of biologic countermeasures, such as neutralizing monoclonal antibodies (mAbs), is essentialfor controlling and containing outbreaks of emerging pathogens where no licensed therapeutic or vaccine isavailable. THE DEFENSE ADVANCED RESEARCHPROJECTS AGENCY 24The P3 program combines expertise in virology, immunology, and cGMP manufacturing to create a fullyintegrated platform for responding rapidly to viral outbreaks with gene-delivered monoclonal antibodies.The DHVI team has succeeded in bringing to our manufacturing unit all aspects of mRNA development andmanufacturing, has isolated numerous SARS-CoV-2 neutralizing antibodies, and has produced an mRNA inour manufacturing unit that encodes one of them. This success makes DHVI a leader in efforts to preparesociety for the next epidemics of infectious agents that might occur.Duke Pandemic Prevention Program (P3)Goal: Halt the spread ofpandemic infections with rapiddevelopment of MedicalCountermeasures.PANDEMIC PREVENTION PLATFORM CONTRACT

The Duke University Regional Biocontainment Laboratory (RBL) is a state-of-the-art biomedical research facilitywith BSL-2 to BSL-3+ biocontainment capabilities dedicated to supporting basic science for the developmentof drugs, diagnostics, and vaccines for emerging infections and biodefense. The facility includes acomprehensive safety and operations program to provide space for both experiments in biocontainment andfor housing animals in an ABSL3 biocontainment setting. Situated on Duke’s west campus and within the DukeHuman Vaccine Institute, the RBL serves as a unique resource for Duke faculty as well as collaborators from allover the Southeast region.Colin Duckett, PhDRBL Co-DirectorColin Duckett, RBL co-director, recently received approximately $14.8 million of NIH funding for modernizing theDuke RBL facility infrastructure. The funding was used to replace critical components of the building air controlsystem with the latest technology to assure continued functionality and to minimize the risk of mechanicalfailures in the future. The integrated security system, including cameras, were replaced to enhance theefficiency of the onsite security and safety teams. A BD FACSymphony S6 Cell Sorter with biosafety cabinet andintegrated aerosol management system was installed in the Biosafety Level 3 (BSL3) flow cytometry laboratory.A Spectral Instruments Lago X live animal imaging system was purchased to expand our imaging services inAnimal Biosafety Level 3 (ABSL3). In addition, a MoleCube CT scanner has been added to provide highthroughput CT imaging in the high-containment space. Steve Slater operates the BD FACSymphony S6 at BSL3.Kristina Riebe prepares the MoleCube CT unit for liveanimal imaging at ABSL3.Modernizing the Duke RBLHerman Staats, PhDRBL Co-Director Scott Alderman RBL Associate DirectorDUKE REGIONALBIOCONTAINMENT LABORATORY25

During the early days of the COVID-19 pandemic, the RBL Safety Team utilized its biosafety expertise andresources to assist the Duke community in its response efforts. Among their initiatives: Initiated a protocol for decontamination of N95 respirators with hydrogen peroxide vapor for safe reuse byDuke Health clinical staff to address worldwide personal protective equipment (PPE) shortage.Developed PPE donning and doffing procedures and provided hands-on training for more than 200 DukeHealth clinical staff.Provided hands-on PPE training for Duke clinical research coordinators who were responsible forcollecting in-home clinical samples. More than 2,000 visits were conducted with no occupationally-acquired infections.Established procedures for the safe handling of SARS-CoV-2 samples in the RBL, and trained more than50 staff who were charged with performing the work.Duke RBL Leads in COVID-19 ResponseThrough the Duke DARPA Pandemic Prevention Platform (P3), DHVI developed a virus propagation platformcapable of rapid and broad screening of virus culture systems for the generation of large-scale virus stocks ofviruses capable of causing new epidemics. This approach involves a “Thaw-and-Infect” eukaryotic cell culturearray comprised of cell types/lines competent for the isolation and high titer growth of a variety of known andunknown viruses.Virus Isolation and IdentificationThe Duke DARPA P3 platform assumes two possible sample input scenarios based on real-world pandemicexperiences (convalescent PBMC/plasma from an infected human or viral isolate/clinical specimen). Ourcurrent and innovative platform approaches to antibody isolation, evolution, screening, and candidateselection utilizes recombinant protein or virus like particles to sort virus specific memory B cells for antibodyisolation. The VH and VL genes of both single pathogen-specific memory B cells are amplified by PCR and thefull Abs produced for study.Antibody Isolation/Characterization/ProductionN95 respirators being decontaminated for reuse. Duke Healthprocessed and reused more than 100,000 N95 respirators tokeep its staff properly protected.26

“DHVI has always been a highly collaborative institute using cutting-edge technology for vaccine design, and,before the pandemic, our efforts were focused on HIV and influenza vaccine development. Since the pandemic,we have been able to rapidly direct our platforms and technologies toward developing COVID-19 vaccines. Oneof the most exciting areas where we have been able to use vaccine technology developed for HIV and apply itto COVID-19 has been our work in developing next generation coronavirus vaccines that will protect againstnew SARS-CoV-2 variants and even coronaviruses within the same family as SARS-CoV-2 to help prevent anew pandemic. We are also very excited about applying the breakthroughs in AI technology to vaccine designso that our work on all vaccines will progress much more rapidly.” - Kevin Wiehe, PhDThe Quantitative Research Division (QRD), co-led by Kevin Wiehe, PhD, and Wes Rountree, has statisticalexpertise ranging from nonparametric and categorical analysis, epidemiologic methods, general andgeneralized linear models, structural equation models, and finite mixture models. Statistical methods areapplied across many scientific teams and programs within DHVI to support vaccine research anddevelopment, as well as lab quality assurance and clinical trials related to vaccine safety. The QRD providesstatistical and computational support for vaccine research (e.g., HIV or SARS-CoV-2), assists in publications,and provides deliverables efficiently. An example of this collaboration relates to the mRNA platform that wasused in Zika vaccine development research at DHVI, which demonstrated that the mRNA vaccine platformcould be utilized for successful vaccine development.DHVI is now harnessing the recent breakthroughs in artificial intelligence (AI) to accelerate vaccine research.The QRD has been applying AI methods to predict the structures of proteins in order to design vaccinecomponents that can precisely guide the immune system to make broadly neutralizing antibodies (bnAbs).The QRD has also used AI to learn the essential features of bnAbs from our large amounts of antibodyrepertoire sequencing data. By learning the essential features, our vaccines can accelerate the developmentof bnAbs because they can be precisely focused to elicit just those essential features. Additionally, the QRDhas increased its productivity and speed of analysis by using AI-assisted computer programming. There isenormous promise in applying AI methods for speeding up vaccine development and the QRD has been at theforefront of utilizing these cutting-edge approaches. QUANTITATIVE RESEARCHDIVISIONKevin Wiehe, PhDDirector of Computational BiologyWes Rountree Director of Biostatistics 27

Joyce Hwang, PhD Mihai Azoitei, PhD Daniel Wrapp, PhD Barton Haynes, MDScott Antonia, Wilton Williams, Joyce Hwang, Mihai Azoitei, Anthony Moody, Edward Patz, Daniel Wrapp, andBarton Haynes have initiated a new program on cancer immunotherapy at DHVI that is a collaboration betweenDHVI and the Duke Cancer Institute. This program has three areas of current research, all aimed at turning theimmune system to attack tumor cells.CANCER IMMUNOTHERAPYScott Antonia, MD, PhDDirector, Duke Cancer Institute Center for Cancer Immunology“We are continuing with this promising initial work and are now expanding the projectwith Williams and DHVI to identify more of these tumor-specific antibodies anddevelop more antibody-based anti-cancer therapeutics.”Anthony Moody and Edward Patz isolated an anti-tumor antibody against lung tumor cells that has proveneffective in animal models for attacking lung tumor cells and reducing tumor size.Joyce Hwang, Mihai Azoitei, Daniel Wrapp, and Barton Haynes, pictured below, have developed a new form ofcancer cell treatment that is proving useful for targeting leukemic cells in animal models, as well as enhancingthe ability of normal immune cells to kill tumor cells.Scott Antonia and Wilton Williams are studying the B cells from non-small cell lung cancers for their ability toproduce novel anti-tumor antibodies and have begun to isolate such antibodies for testing in animal models.This immune treatment is an antibody that targets a molecule called HLA-E on tumor cells and in doing so,enhances normal CD8+ T cell and natural killer (NK) cell ability to kill tumor cells. This treatment is also beingused to attack latently HIV-infected CD4+ T cells as well as latently TB-infected macrophages. This is a newarea of cancer immunotherapy using antibodies to release T cells and NK cells to kill tumor cells by binding toa molecule called HLA-E.28

DHVI partnered with Meredith College in Raleigh, NC, to develop thePipeline Enhancement to Retain Students via the Inclusive STEMTraining (PERSIST) program. The PERSIST program aims to exposehigh school students to STEM careers (science, technology, engineering, and math) in hopes ofincreasing their knowledge of and willingness to pursue careers in STEM. The PERSIST curriculum has beendeveloped by DHVI and Meredith faculty and will be taken to area high schools for their use in educatingstudents on STEM topics and helping them understand the science and manufacturing activities that are inDHVI. DHVI faculty have presented seminars at Meredith College on DHVI research, as well as career and jobopportunities.The Duke Human Vaccine Institute's Diversity, Equity, and Inclusion(DEI) committee is dedicated to exploring topics that are importantfor helping the DHVI community be a welcoming and equitable placefor all DHVI members. The committee hosts informational andtraining seminars on such topics as disabilities, microaggressions,workplace safety, and mental health awareness.DHVI DIVERSITY, EQUITY,AND INCLUSION ACTIVITIESSaunders poses with PERSIST programstudents at Meredith College. A long-term goal of DHVI is to achieve fundingfor internships at DHVI for under-represented minority students.29Kevin Saunders, PhDDiversity, Equity, and InclusionCommittee ChairpersonEducationSTEM Career PipelineOutreachDHVI’s DEI committee arranged for DHVI employees to serve their community by packing meals for familes inneed around the Triangle area during the 2023 Martin Luther King MLK Day of Service.In partnership withlocal rotary clubs,Duke Universitystudents, faculty, andstaff helped packmore than 30,000meals, benefittingNorth Carolina foodbanks.Saunders (left)pictured with DukeUniversity PresidentVincent Price(middle) and DEIcommittee memberElizabeth Van Itallie(right).

Mentoring and collaborative research,Research seminars, lectures, and independent research presentations,Scientific writing and presentation workshops,Career development,Fostering community,Annual trainee retreat, andJournal club: a weekly gathering to discuss scientific journal articles amongtrainees and staff.53%Published2Early stage investigators9Graduate studentsPostdocs/housestaff/researchassociates281MD/PhD8UndergraduatesMedical student138%49%51%PROGRAMSNAPSHOTMales FemalesThe goal of the DHVI Training and Mentoring Program (DTMP) is to expand eachtrainee's knowledge base and confidence through mentorship, customizedcurricula, and access to state-of-the-art technology. The DTMP supports thedevelopment of DHVI trainees into independent scientific professionals,engaging trainees beyond its outstanding training environment and researchexperiences by organizing service and fellowship events outside of the lab.Pictured with theirtrainees, co-directorsMaria Blasi, PhD (farright, front row), andWilton Williams, PhD(far left, front row),are recipients of theDuke UniversitySchool of Medicine’s2023 faculty awardfor Early CareerMentoring in BasicScience. 30DHVI TRAININGAND MENTORING PROGRAMFirst AuthorsOur Taking Science to the Streets (TSTTS) meeting launched in 2020. TSTTS is abi-weekly meeting where guests and trainees discuss the science behind thepolicies for managing infectious diseases and focus on how to effectivelycommunicate science to the general public. Meetings feature guests fromacademia, industry, government agencies like the FDA, and local communities.Other critical components of the DTMP include:

This group of faculty is representative of the next generation of DHVI members recruited todevelop new drugs, diagnostics, and vaccines for the future. Pictured left to right: Maria Blasi,PhD, Kevin Saunders, PhD, Munir Alam, PhD, Barton Haynes, MD, Priyamvada Acharya, PhD,Kevin Wiehe, PhD, Wilton Williams, PhD.Duke Human Vaccine Institute scientists have offered proof of concept for a preventative vaccinestrategy that aims to guide the immune system to create the desired antibodies that neutralizepathogenic viruses. With this knowledge to “engineer the immune system,” DHVI is using thisstrategy against numerous global infectious threats with our pandemic preparedness rapidresponse programs. DHVI maintains a robust translational pipeline of basic scientists, manufacturingcapabilities for iterative phase 1 clinical trials, and the clinical support to carry out clinical trials inorder to respond rapidly to emerging threats. Team-based big science has been a hallmark of DHVIand we will use our cooperative mode of research to continue to successfully face new globalinfectious disease threats. WHERE WE ARE HEADED31

Contact us!2 Genome Court, MSRBIIDUMC 103020Durham, NC 27710dhvi.duke.edu | 919-684-5836LinkedIn.com/company/thedhviEditor in Chief: Kelly WrightCopyright 2024Learn the many ways you can help by contactingJ. Steven Barnes, Interim Vice President of Duke Health Development and Alumni Affairssteven.barnes@duke.edu or (919) 407-2896GIFTS OF SUPPORTFOR DHVIOur mission in the Duke Human VaccineInstitute is to perform the basic and translationalwork to solve problems in society, yet theproducts of such research may not be profitableor the enabling technology is not known. Formore than 30 years, DHVI has been at theforefront of vaccine research. Our decades ofresearch into HIV and other viruses have built thefoundation for current COVID-19 vaccines. Nowwe are making key breakthroughs in the race tocreate pancoronavirus vaccines to protectagainst new SARS-CoV-2 variants and futurecoronaviruses, and to develop a successful HIVvaccine.Infectious diseases will continue to emerge and each newdisease has the potential to endanger society. The level ofpreparation required to address an emerging threat isenormous and must be deployable without delay as soon asa threat emerges. Our challenge is to be ready.Private philanthropy is absolutely essential to our ability to rapidly conduct thekind of innovative exploration that enables our ability to rapidly respond to anynew infectious disease threats.Supports trainees and faculty to develop the next generation of scientists to meet future pandemic threats.Enables acquisition of new technology to rapidly respond to outbreaks and emerging threats.Provides funds for immediate responses to new infections and to follow-up and develop new discoveriesrather than to wait a year to receive new grants or contracts.Provides critical infrastructure for the safe handling of highly complex pathogens.Supports the manufacturing of antibodies and vaccines for clinical trials.Your gift:With your help, we will be ready to prevent and treat diseases of global importance, while working to eliminatehealth disparities and train the next generation of scientists.