Yunda Huang1, Kelly E Seaton2, Martin Casapia3, Laura Polakowski4, Stephen C De Rosa5, Kristen Cohen5, Chenchen Yu5, Marnie Elizaga5, Carmen Paez5, Maurine D Miner5, Colleen F Kelley6, Janine Maenza5, Michael Keefer7, Javier R Lama8, Magdalena Sobieszczyk9, Susan Buchbinder10, Lindsey R Baden11, Carter Lee12, Vineeta Gulati12, Faruk Sinangil12, David Montefiori13, M Juliana McElrath5, Georgia D Tomaras2, Harriet L Robinson14, Paul Goepfert15. 1. Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Department of Global Health, University of Washington, Seattle, WA, USA. 2. Duke Center for Human Systems Immunology, Duke University Departments of Surgery, Immunology, Pathology, Molecular Genetics and Microbiology, Durham, NC, USA. 3. Asociacion Civil Selva Amazonica, Universidad Nacional de la Amazonia, Iquitos, Peru. Urbanizacion Jardin 27, Iquitos, Peru. Electronic address: mcasapia@acsaperu.org. 4. Division of AIDS, NIAID, Rockville, MD, USA. 5. Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. 6. Department of Medicine, Emory University, Atlanta, GA, USA. 7. Infectious Diseases Division, Department of Medicine, University of Rochester, Rochester, NY, USA. 8. Asociacion Civil Impacta Salud y Educacion, Lima, Peru. 9. Department of Medicine, Division of Infectious Diseases, Columbia University Irving Medical Center, NYC, USA. 10. Bridge HIV, San Francisco Department of Public Health, San Francisco, CA, USA. 11. Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. 12. Global Solutions for Infectious Diseases, Lafayette, CA, USA. 13. Department of Surgery and Duke Human Vaccine Institute, Duke University, Durham, NC, USA. 14. GeoVax, Atlanta, GA, USA. 15. Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA. Electronic address: pgoepfert@uabmc.edu.
Abstract
BACKGROUND: Eliciting durable humoral immunity with sufficient breadth and magnitude is important for HIV-1 vaccine design. The HVTN 114 vaccine trial evaluated different boost regimens administered after a 7-year rest period in participants previously enrolled in HVTN 205, who received either three MVA/HIV62B (MMM) or two DNA and two MVA/HIV62B (DDMM) injections; both vaccines expressed multiple HIV-1 antigens in non-infectious virus-like-particles. The primary objective of HVTN 114 was to assess the impact of a heterologous gp120 protein AIDSVAX B/E boost on the magnitude, breadth and durability of vaccine-induced immune responses. METHODS: We enrolled 27 participants from HVTN 205 into five groups. Eight participants who previously received MMM were randomized and boosted with either MVA/HIV62B alone (T1; n = 4) or MVA/HIV62B and AIDSVAX B/E (T2; n = 4). Nineteen participants who received DDMM were randomized and boosted with MVA/HIV62B alone (T3; n = 6), MVA/HIV62B and AIDSVAX B/E (T4; n = 6), or AIDSVAX B/E alone (T5; n = 7). Boosts were at months 0 and 4. Participants were followed for safety and immunogenicity for 10 months and were pooled for analysis based on the regimen: MVA-only (T1 + T3), MVA + AIDSVAX (T2 + T4), and AIDSVAX-only (T5). RESULTS: All regimens were safe and well-tolerated. Prior to the boost vaccination, binding antibody and CD4+T-cell responses were observed 7 years after HVTN 205 vaccinations. Late boosting with AIDSVAX, with or without MVA, resulted in high binding antibody responses to gp120 and V1V2 epitopes, with increased magnitude and breadth compared to those observed in HVTN 205. Late boosting with MVA, with or without AIDSVAX, resulted in increased gp140 and gp41 antibody responses and higher CD4+T-cell responses to Env and Gag. CONCLUSIONS: Late boosting with AIDSVAX, alone or in combination with MVA, can broaden binding antibody responses and increase T-cell responses even years following the original MVA/HIV62B with or without DNA-priming vaccine. Published by Elsevier Ltd.
BACKGROUND: Eliciting durable humoral immunity with sufficient breadth and magnitude is important for HIV-1 vaccine design. The HVTN 114 vaccine trial evaluated different boost regimens administered after a 7-year rest period in participants previously enrolled in HVTN 205, who received either three MVA/HIV62B (MMM) or two DNA and two MVA/HIV62B (DDMM) injections; both vaccines expressed multiple HIV-1 antigens in non-infectious virus-like-particles. The primary objective of HVTN 114 was to assess the impact of a heterologous gp120 protein AIDSVAX B/E boost on the magnitude, breadth and durability of vaccine-induced immune responses. METHODS: We enrolled 27 participants from HVTN 205 into five groups. Eight participants who previously received MMM were randomized and boosted with either MVA/HIV62B alone (T1; n = 4) or MVA/HIV62B and AIDSVAX B/E (T2; n = 4). Nineteen participants who received DDMM were randomized and boosted with MVA/HIV62B alone (T3; n = 6), MVA/HIV62B and AIDSVAX B/E (T4; n = 6), or AIDSVAX B/E alone (T5; n = 7). Boosts were at months 0 and 4. Participants were followed for safety and immunogenicity for 10 months and were pooled for analysis based on the regimen: MVA-only (T1 + T3), MVA + AIDSVAX (T2 + T4), and AIDSVAX-only (T5). RESULTS: All regimens were safe and well-tolerated. Prior to the boost vaccination, binding antibody and CD4+T-cell responses were observed 7 years after HVTN 205 vaccinations. Late boosting with AIDSVAX, with or without MVA, resulted in high binding antibody responses to gp120 and V1V2 epitopes, with increased magnitude and breadth compared to those observed in HVTN 205. Late boosting with MVA, with or without AIDSVAX, resulted in increased gp140 and gp41 antibody responses and higher CD4+T-cell responses to Env and Gag. CONCLUSIONS: Late boosting with AIDSVAX, alone or in combination with MVA, can broaden binding antibody responses and increase T-cell responses even years following the original MVA/HIV62B with or without DNA-priming vaccine. Published by Elsevier Ltd.
Entities:
Keywords:
AIDSVAX; DNA Vaccine; HIV vaccine; Late boost; MVA vaccine; V1V2 antibody
Authors: Paul A Goepfert; Marnie L Elizaga; Kelly Seaton; Georgia D Tomaras; David C Montefiori; Alicia Sato; John Hural; Stephen C DeRosa; Spyros A Kalams; M Juliana McElrath; Michael C Keefer; Lindsey R Baden; Javier R Lama; Jorge Sanchez; Mark J Mulligan; Susan P Buchbinder; Scott M Hammer; Beryl A Koblin; Michael Pensiero; Chris Butler; Bernard Moss; Harriet L Robinson Journal: J Infect Dis Date: 2014-01-07 Impact factor: 5.226
Authors: Scott D Neidich; Youyi Fong; Shuying S Li; Daniel E Geraghty; Brian D Williamson; William Chad Young; Derrick Goodman; Kelly E Seaton; Xiaoying Shen; Sheetal Sawant; Lu Zhang; Allan C deCamp; Bryan S Blette; Mengshu Shao; Nicole L Yates; Frederick Feely; Chul-Woo Pyo; Guido Ferrari; Ian Frank; Shelly T Karuna; Edith M Swann; John R Mascola; Barney S Graham; Scott M Hammer; Magdalena E Sobieszczyk; Lawrence Corey; Holly E Janes; M Juliana McElrath; Raphael Gottardo; Peter B Gilbert; Georgia D Tomaras Journal: J Clin Invest Date: 2019-11-01 Impact factor: 14.808
Authors: Xiaoying Shen; Fatima Laher; Zoe Moodie; Arthur S McMillan; Rachel L Spreng; Peter B Gilbert; Ying Huang; Nicole L Yates; Nicole Grunenberg; M Juliana McElrath; Mary Allen; Michael Pensiero; Vijay L Mehra; Olivier Van Der Meeren; Susan W Barnett; Sanjay Phogat; Glenda E Gray; Linda-Gail Bekker; Lawrence Corey; Georgia D Tomaras Journal: Sci Rep Date: 2020-02-07 Impact factor: 4.379
Authors: Kelly E Seaton; Lamar Ballweber; Audrey Lan; Michele Donathan; Sean Hughes; Lucia Vojtech; M Anthony Moody; Hua-Xin Liao; Barton F Haynes; Christine G Galloway; Barbra A Richardson; Salim Abdool Karim; Charlene S Dezzutti; M Juliana McElrath; Georgia D Tomaras; Florian Hladik Journal: PLoS One Date: 2014-07-23 Impact factor: 3.240
Authors: Fatima Laher; Zoe Moodie; Kristen W Cohen; Nicole Grunenberg; Linda-Gail Bekker; Mary Allen; Nicole Frahm; Nicole L Yates; Lynn Morris; Mookho Malahleha; Kathryn Mngadi; Brodie Daniels; Craig Innes; Kevin Saunders; Shannon Grant; Chenchen Yu; Peter B Gilbert; Sanjay Phogat; Carlos A DiazGranados; Marguerite Koutsoukos; Olivier Van Der Meeren; Carter Bentley; Nonhlanhla N Mkhize; Michael N Pensiero; Vijay L Mehra; James G Kublin; Lawrence Corey; David C Montefiori; Glenda E Gray; M Juliana McElrath; Georgia D Tomaras Journal: PLoS Med Date: 2020-02-24 Impact factor: 11.069