Research Areas at the Duke Vaccine and Trials Unit

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The DVTU is a member of the Centers for Disease Control and Prevention (CDC) sponsored Clinical Immunization Safety Assessment (CISA) project. As a site for this national network, which includes eight academic medical centers, Duke assists safety experts from the CDC’s Immunization Safety Office (ISO) in providing a comprehensive vaccine safety public health service to the nation.

The mission of the CISA project is to improve understanding of adverse events following immunization (AEFIs) at the individual-patient level. CISA provides consultation to U.S. healthcare providers with complex vaccine safety questions. In addition, CISA conducts clinical research aimed at addressing vaccine safety questions. The DVTU has conducted numerous studies assessing vaccine safety in special populations and evaluating potential strategies to prevent AEFIs. The DHVI plays a critical role by providing the necessary infrastructure to conduct laboratory assessments for CISA sponsored studies.

Selected Publications

  • Fortner KB, Swamy GK, Broder KR, Jimenez-Truque N, Zhu Y, Moro PL, Liang J, Walter EB, Heine RP, Moody MA, Yoder S, Edwards KM. Reactogenicity and immunogenicity of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) in pregnant and nonpregnant women. Vaccine. 2018 Oct 8;36(42):6354-6360. doi: 10.1016/j.vaccine.2018.07.012. Epub 2018 Sep 13. PMID: 30219367; PMCID: PMC6675450.
  • Schmader KE, Liu CK, Harrington T, Rountree W, Auerbach H, Walter EB, Barnett ED, Schlaudecker EP, Todd CA, Poniewierski M, Staat MA, Wodi P, Broder KR. Safety, Reactogenicity, and Health-Related Quality of Life After Trivalent Adjuvanted vs Trivalent High-Dose Inactivated Influenza Vaccines in Older Adults: A Randomized Clinical Trial. JAMA Netw Open. 2021 Jan 4;4(1):e2031266. doi: 10.1001/jamanetworkopen.2020.31266. PMID: 33443580; PMCID: PMC7809592.
  • Schmader KE, Liu CK, Flannery B, Rountree W, Auerbach H, Barnett ED, Schlaudecker EP, Todd CA, Poniewierski M, Staat MA, Harrington T, Li R, Broder KR, Walter EB. Immunogenicity of adjuvanted versus high-dose inactivated influenza vaccines in older adults: a randomized clinical trial. Immun Ageing. 2023 Jul 1;20(1):30. doi: 10.1186/s12979-023-00355-7. PMID: 37393237; PMCID: PMC10314373.
  • Sokolow AG, Stallings AP, Kercsmar C, Harrington T, Jimenez-Truque N, Zhu Y, Sokolow K, Moody MA, Schlaudecker EP, Walter EB, Staat MA, Broder KR, Creech CB. Safety of Live Attenuated Influenza Vaccine in Children With Asthma. Pediatrics. 2022 Apr 1;149(4):e2021055432. doi: 10.1542/peds.2021-055432. Erratum in: Pediatrics. 2022 Aug 1;150(2): PMID: 35342923.
  • Walter EB, Klein NP, Wodi AP, Rountree W, Todd CA, Wiesner A, Duffy J, Marquez PL, Broder KR. Fever After Influenza, Diphtheria-Tetanus-Acellular Pertussis, and Pneumococcal Vaccinations. Pediatrics. 2020 Mar;145(3):e20191909. doi: 10.1542/peds.2019-1909. Epub 2020 Feb 6. PMID: 32029684; PMCID: PMC7055925.

The DVTU serves as one of two Clinical Cores for the National Institute of Allergy and Infectious Diseases (NIAID) Collaborative Influenza Vaccine Innovations Centers (CIVICs). The CIVICs program was created by NIAID to develop improved influenza vaccines that provide broader and longer lasting protection. As a CIVICs Clinical Core, DVTU work is currently focused on evaluating promising next generation influenza vaccine candidates in Phase I and Phase I/II clinical trials. The unit is also conducting human influenza challenge studies aimed at determining the optimal dose of influenza challenge virus strains. Ultimately, we aim to be able to rapidly test promising new influenza vaccines using the human influenza challenge model.

In addition, our CIVICs work is also focused on harmonizing endpoint assays used to evaluate influenza vaccine trials and human influenza challenge studies. Through these efforts, we hope to learn more about correlates of protection from influenza and durable immunity. The Duke Human Vaccine Institute (DHVI) Accessioning Unit & Biorepository is further charged with managing the biological samples obtained from CIVICS clinical trials and challenge studies to enable future research.

Selected Publications

  • Bernstein DI, Guptill J, Naficy A, Nachbagauer R, Berlanda-Scorza F, Feser J, Wilson PC, Solórzano A, Van der Wielen M, Walter EB, Albrecht RA, Buschle KN, Chen YQ, Claeys C, Dickey M, Dugan HL, Ermler ME, Freeman D, Gao M, Gast C, Guthmiller JJ, Hai R, Henry C, Lan LY, McNeal M, Palm AE, Shaw DG, Stamper CT, Sun W, Sutton V, Tepora ME, Wahid R, Wenzel H, Wohlbold TJ, Innis BL, García-Sastre A, Palese P, Krammer F. Immunogenicity of chimeric haemagglutinin-based, universal influenza virus vaccine candidates: interim results of a randomised, placebo-controlled, phase 1 clinical trial. Lancet Infect Dis. 2020 Jan;20(1):80-91. doi: 10.1016/S1473-3099(19)30393-7. Epub 2019 Oct 17. PMID: 31630990; PMCID: PMC6928577.
  • Ortiz JR, Bernstein DI, Hoft DF, Woods CW, McClain MT, Frey SE, Brady RC, Bryant C, Wegel A, Frenck RW, Walter EB, Abate G, Williams SR, Atmar RL, Keitel WA, Rouphael N, Memoli MJ, Makhene MK, Roberts PC, Neuzil KM; Influenza Controlled Human Infection Study Group Members. A Multi-Center, Controlled Human Infection Study of Influenza A (H1N1)pdm09 in Healthy Adults. J Infect Dis. 2023 Jan 26:jiad021. doi: 10.1093/infdis/jiad021. Epub ahead of print. PMID: 36702771.
  • Sawant S, Gurley SA, Overman RG, Sharak A, Mudrak SV, Oguin T 3rd, Sempowski GD, Sarzotti-Kelsoe M, Walter EB, Xie H, Pasetti MF, Moody MA, Tomaras GD. H3N2 influenza hemagglutination inhibition method qualification with data driven statistical methods for human clinical trials. Front Immunol. 2023 Apr 6;14:1155880. doi: 10.3389/fimmu.2023.1155880. PMID: 37090729; PMCID: PMC10117676.


Led by Dr. Christopher Woods, Professor of Medicine, the DVTU has conducted numerous studies in our emerging infection/biomarkers department. Dr. Woods serves as Chief of Infectious Diseases and clinical microbiology, and hospital epidemiologist for the Durham VA Medical Center. Dr. Woods is board-certified in internal medicine, infectious diseases, and medical microbiology. His research focuses on the development of novel diagnostic approaches to infectious disease and the potential for interspecies transmission of pathogens. His genomic approach to harnessing the host response for diagnosis of infectious diseases has been called a paradigm shift in the field.
Dr. Woods is a partner in the Southeastern Center for Emerging Biological Threats, core PI of the Southeastern Research Center for Excellence on Emerging Infections and Biodefense, and a leader in the NIH-funded Vaccine and Therapeutics Evaluation Unit at Duke.

During the last two decades the DVTU has assisted with national pandemic preparedness and response. Through its work with NIAID’s Vaccine and Treatment Evaluation Units (VTEUs), the DVTU has evaluated influenza vaccines aimed at the control and prevention of novel influenza viruses of special concern. DVTU studies have included evaluations of vaccines against avian influenza H5 and H7 viruses and swine influenza H3N2 variant virus. Several of these studies evaluated vaccines using novel adjuvants. During 2009, the DVTU worked alongside the VTEUs to rapidly evaluate influenza vaccines aimed at preventing pandemic influenza caused by a novel H1N1 virus. Studies assessed pdm09H1N1 influenza vaccine in children, adults, older adults and pregnant women. Most recently, the DVTU has conducted multiple adult and pediatric COVID-19 vaccine studies aimed at preventing severe illness due to SARS-CoV-2 infection.

Selected Publications:

  • Belshe RB, Frey SE, Graham IL, Anderson EL, Jackson LA, Spearman P, Edupuganti S, Mulligan MJ, Rouphael N, Winokur P, Dolor RJ, Woods CW, Walter EB, Chen WH, Turley C, Edwards KM, Creech CB, Hill H, Bellamy AR; National Institute of Allergy and Infectious Diseases–Funded Vaccine and Treatment Evaluation Units. Immunogenicity of avian influenza A/Anhui/01/2005(H5N1) vaccine with MF59 adjuvant: a randomized clinical trial. JAMA. 2014 Oct 8;312(14):1420-8. doi: 10.1001/jama.2014.12609. PMID: 25291578.
  • Branche AR, Rouphael NG, Losada C, Baden LR, Anderson EJ, Luetkemeyer AF, Diemert DJ, Winokur PL, Presti RM, Kottkamp AC, Falsey AR, Frey SE, Rupp R, Bäcker M, Novak RM, Walter EB, Jackson LA, Little SJ, Immergluck LC, Mahgoub SM, Whitaker JA, Babu TM, Goepfert PA, Fusco DN, Atmar RL, Posavad CM, Netzl A, Smith DJ, Telu K, Mu J, Makowski M, Makhene MK, Crandon S, Montefiori DC, Roberts PC, Beigel JH. Immunogenicity of the BA.1 and BA.4/BA.5 Severe Acute Respiratory Syndrome Coronavirus 2 Bivalent Boosts: Preliminary Results From the COVAIL Randomized Clinical Trial. Clin Infect Dis. 2023 Aug 22;77(4):560-564. doi: 10.1093/cid/ciad209. PMID: 37036397; PMCID: PMC10443997.
  • Chen WH, Winokur PL, Edwards KM, Jackson LA, Wald A, Walter EB, Noah DL, Wolff M, Kotloff KL; Pandemic H1N1 Vaccine Adult Study Group. Phase 2 assessment of the safety and immunogenicity of two inactivated pandemic monovalent H1N1 vaccines in adults as a component of the U.S. pandemic preparedness plan in 2009. Vaccine. 2012 Jun 13;30(28):4240-8. doi: 10.1016/j.vaccine.2012.04.044. Epub 2012 Apr 23. PMID: 22537984; PMCID: PMC3490194.
  • Neuzil KM, Anderson EJ, Frenck RW, Frey SE, Walter EB, Rupp R, Rotrosen ET, Rouphael NG, Brady RC, Graham I, Schmader KE, Porterfield L, Ortiz JR, Swamy GK, El Sahly HM, Jeevan T, Sitaula R, Wegel A, Webby RJ, Bryant C; Influenza A/H5N8 Virus Vaccine Group. Safety and Immunogenicity of Influenza A/H5N8 Virus Vaccine in Healthy Adults: Durability and Cross-reactivity of Antibody Responses. Clin Infect Dis. 2023 Jan 5:ciac982. doi: 10.1093/cid/ciac982. Epub ahead of print. PMID: 36610728.
  • Walter 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, Munjal I, 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 the BNT162b2 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. Epub 2021 Nov 9. PMID: 34752019; PMCID: PMC8609605.

Led by Duke Pediatrician, Dr. Emmanuel Walter and Dr. Michael Smith, chief of Duke Division of Pediatric Infectious Diseases, the DVTU has a long standing interest in studying vaccines designed to prevent childhood infections. While a large number of our studies helped to assess these vaccines prior to their receiving approval for use in children by the US Food and Drug Administration, we have also conducted numerous studies of vaccines following their approval. We are proud that many of the vaccines we have studied are now included in the schedule of routinely recommended vaccines for children and adolescents. Our group worked on vaccines to prevent meningitis, hepatitis, infantile diarrhea, influenza, and chicken pox in young children. In addition, we conducted studies on vaccines to prevent whooping cough, human papillomavirus and meningococcal infection in adolescents. We are currently engaged in studies to prevent RSV infection, which is the most common cause of pneumonia and bronchiolitis in young infants.

Selected Publications

  • Libster R, McNeal M, Walter EB, Shane AL, Winokur P, Cress G, Berry AA, Kotloff KL, Sarpong K, Turley CB, Harrison CJ, Pahud BA, Marbin J, Dunn J, El-Khorazaty J, Barrett J, Edwards KM; VTEU Rotavirus Vaccine Study Work Group. Safety and Immunogenicity of Sequential Rotavirus Vaccine Schedules. Pediatrics. 2016 Feb;137(2):e20152603. doi: 10.1542/peds.2015-2603. Epub 2016 Jan 28. PMID: 26823540; PMCID: PMC4732359.
  • Russell K, Dunne EF, Kemper AR, Dolor RJ, Unger ER, Panicker G, Markowitz LE, Walter EB. Antibody responses among adolescent females receiving the quadrivalent HPV vaccine series corresponding to standard or non-standard dosing intervals. Vaccine. 2015 Apr 15;33(16):1953-8. doi: 10.1016/j.vaccine.2015.02.058. Epub 2015 Mar 3. PMID: 25744229.
  • Smith MJ, Jordanov E, Sheng X, Tsang PH. Safety and Immunogenicity of DTaP5-IPV Compared With DTaP5 Plus IPV as the Fifth Dose in Children 4-6 Years of Age. Pediatr Infect Dis J. 2017 Mar;36(3):319-325. doi: 10.1097/INF.0000000000001427. PMID: 27879555.
  • Walter EB, Neuzil KM, Zhu Y, Fairchok MP, Gagliano ME, Monto AS, Englund JA. Influenza vaccine immunogenicity in 6- to 23-month-old children: are identical antigens necessary for priming? Pediatrics. 2006 Sep;118(3):e570-8. doi: 10.1542/peds.2006-0198. PMID: 16950948.

The DVTU has a long-standing collaboration with the Duke Perinatal Research Center (DPRC), whose primary mission is to improve the health of pregnant people and their families. One of DPRC’s areas of expertise is infectious disease research in pregnancy including maternal immunization aimed at preventing maternal, fetal and neonatal infections. We have conducted numerous investigational and observational studies in pregnancy including novel vaccines to prevent maternal influenza and COVID-19 as well as infant influenza, pertussis, RSV, and Group B strep. We have proudly contributed to the first U.S. study of H1N1 vaccine in pregnancy during the 2009-10 pandemic and studies of Tdap in pregnancy at the height of the pertussis resurgence in 2008-2012 that informed guidelines for Tdap administration in pregnancy. We are currently engaged in studies of licensed influenza and COVID-19 vaccines to evaluate safety, timing of vaccine, and factors impacting immunogenicity in mothers and infants.

Selected Publications

  • Madhi SA, Polack FP, Piedra PA, Munoz FM, Trenholme AA, Simões EAF, Swamy GK, Agrawal S, Ahmed K, August A, Baqui AH, Calvert A, Chen J, Cho I, Cotton MF, Cutland CL, Englund JA, Fix A, Gonik B, Hammitt L, Heath PT, de Jesus JN, Jones CE, Khalil A, Kimberlin DW, Libster R, Llapur CJ, Lucero M, Pérez Marc G, Marshall HS, Masenya MS, Martinón-Torres F, Meece JK, Nolan TM, Osman A, Perrett KP, Plested JS, Richmond PC, Snape MD, Shakib JH, Shinde V, Stoney T, Thomas DN, Tita AT, Varner MW, Vatish M, Vrbicky K, Wen J, Zaman K, Zar HJ, Glenn GM, Fries LF; Prepare Study Group. Respiratory Syncytial Virus Vaccination during Pregnancy and Effects in Infants. N Engl J Med. 2020 Jul 30;383(5):426-439. doi: 10.1056/NEJMoa1908380. PMID: 32726529; PMCID: PMC7299433.
  • Munoz FM, Bond NH, Maccato M, Pinell P, Hammill HA, Swamy GK, Walter EB, Jackson LA, Englund JA, Edwards MS, Healy CM, Petrie CR, Ferreira J, Goll JB, Baker CJ. Safety and immunogenicity of tetanus diphtheria and acellular pertussis (Tdap) immunization during pregnancy in mothers and infants: a randomized clinical trial. JAMA. 2014 May 7;311(17):1760-9. doi: 10.1001/jama.2014.3633. Erratum in: JAMA. 2017 Jan 24;317(4):442. Erratum in: JAMA. 2017 Jan 24;317(4):441-442. PMID: 24794369; PMCID: PMC4333147.
  • Swamy GK, Metz TD, Edwards KM, Soper DE, Beigi RH, Campbell JD, Grassano L, Buffi G, Dreisbach A, Margarit I, Karsten A, Henry O, Lattanzi M, Bebia Z. Safety and immunogenicity of an investigational maternal trivalent group B streptococcus vaccine in pregnant women and their infants: Results from a randomized placebo-controlled phase II trial. Vaccine. 2020 Oct 14;38(44):6930-6940. doi: 10.1016/j.vaccine.2020.08.056. Epub 2020 Sep 1. PMID: 32883555.

Led by Dr. Kenneth Schmader, Professor of Medicine, former Chief Division of Geriatrics in the Department of Medicine, the DVTU has conducted numerous studies in older adult populations. These studies assessed vaccines prior to and after FDA approval and CDC clinical recommendations. The studies include pre-clinical research and clinical trials of the immunogenicity, safety, reactogenicity, clinical efficacy and effectiveness of the live zoster vaccine, recombinant zoster vaccine, standard dose, high dose and adjuvanted influenza vaccines, COVID-19, RSV and pneumococcal vaccines in older adults. The zoster and influenza vaccine studies include innovative measures of functional status and quality of life which are critically important outcomes in older adults.

Selected Publications

  • Curran D, Andrew MK, Levin MJ, Turriani E, Matthews S, Fogarty C, Klein NP, Grupping K, Oostvogels L, Schmader KE. Evaluation of two frailty indices, with practical application in a vaccine clinical trial. Hum Vaccin Immunother. 2019;15(12):2960-2968. doi: 10.1080/21645515.2019.1622974. Epub 2019 Jun 21. PMID: 31157595; PMCID: PMC6930102.
  • Schmader KE, Levin MJ, Chen M, Matthews S, Riley ME, Woo W, Hervé C, Grupping K, Schuind AE, Oostvogels L, Curran D. Impact of Reactogenicity After Two Doses of Recombinant Zoster Vaccine Upon Physical Functioning and Quality of Life: An Open Phase III Trial in Older Adults. J Gerontol A Biol Sci Med Sci. 2021 Feb 25;76(3):485-490. doi: 10.1093/gerona/glaa127. PMID: 32530462; PMCID: PMC7907492.
  • Winokur P, El Sahly HM, Mulligan MJ, Frey SE, Rupp R, Anderson EJ, Edwards KM, Bernstein DI, Schmader K, Jackson LA, Chen WH, Hill H, Bellamy A; DMID 13-0034 H7N9 Vaccine Study Group. Immunogenicity and safety of different dose schedules and antigen doses of an MF59-adjuvanted H7N9 vaccine in healthy adults aged 65 years and older. Vaccine. 2021 Feb 22;39(8):1339-1348. doi: 10.1016/j.vaccine.2020.11.051. Epub 2021 Jan 21. PMID: 33485646; PMCID: PMC8504682.

The U.S. Flu Vaccine Effectiveness (VE) network is designed to provide estimates of clinical effectiveness of licensed flu vaccines by age group and by influenza (flu) virus type and subtype.

The network consists of seven study sites and one coordinating center (Duke University) spread across the United States:

  • Arizona
  • Michigan
  • Missouri
  • North Carolina - Coordinating Center
  • Ohio
  • Pennsylvania
  • Texas
  •  Washington

The study uses a test-negative design which compares vaccination rates among persons with confirmed flu illness versus persons with similar illness who do not have flu based on laboratory tests. More information on the study methods used by the U.S. Flu VE Network is available at Study Design Factors.