EBioMedicine (Oct 2024)
Immune correlates analysis of the Imbokodo (HVTN 705/HPX2008) efficacy trial of a mosaic HIV-1 vaccine regimen evaluated in Southern African people assigned female sex at birth: a two-phase case-control studyResearch in context
- Avi Kenny,
- Janine van Duijn,
- One Dintwe,
- Jack Heptinstall,
- Randy Burnham,
- Sheetal Sawant,
- Lu Zhang,
- Dieter Mielke,
- Sharon Khuzwayo,
- Faatima Laher Omar,
- Sherry Stanfield-Oakley,
- Taylor Keyes,
- Brooke Dunn,
- Derrick Goodman,
- Youyi Fong,
- David Benkeser,
- Rodger Zou,
- John Hural,
- Ollivier Hyrien,
- Michal Juraska,
- Alex Luedtke,
- Lars van der Laan,
- Elena E. Giorgi,
- Craig Magaret,
- Lindsay N. Carpp,
- Laura Pattacini,
- Tom van de Kerkhof,
- Bette Korber,
- Wouter Willems,
- Leigh H. Fisher,
- Hanneke Schuitemaker,
- Edith Swann,
- James G. Kublin,
- Maria G. Pau,
- Susan Buchbinder,
- Frank Tomaka,
- Steven Nijs,
- Ludo Lavreys,
- Huub C. Gelderblom,
- Lawrence Corey,
- Kathryn Mngadi,
- Glenda E. Gray,
- Erica Borducchi,
- Jenny Hendriks,
- Kelly E. Seaton,
- Susan Zolla-Pazner,
- Dan H. Barouch,
- Guido Ferrari,
- Stephen C. De Rosa,
- M Juliana McElrath,
- Erica Andersen-Nissen,
- Daniel J. Stieh,
- Georgia D. Tomaras,
- Peter B. Gilbert,
- Jon Allagappen,
- Jessica Andriesen,
- Alison Ayres,
- Saman Baral,
- Linda-Gail Bekker,
- Asiphe Besethi,
- Caroline Borremans,
- Esmee Braams,
- Caroline Brackett,
- William Brumskine,
- Roma Chilengi,
- Rachel Choi,
- Thozama Dubula,
- Jaiden Seongmi Dumas,
- Brooke Dunn,
- Radhika Etikala,
- Zelda Euler,
- Sarah Everett,
- Nigel Garrett,
- Huub Gelderblom,
- Katherine Gill,
- Kevin Gillespie,
- Dimitri Goedhart,
- Erik Goosmann,
- Shannon Grant,
- Ellie Hands,
- Barton Haynes,
- Bronwill Herringer,
- Zaheer Hoosain,
- Mina Hosseinipour,
- Portia Hunidzarira,
- Julia Hutter,
- Mubiana Inambao,
- Craig Innes,
- Taylor Keyes,
- William Kilembe,
- Philippus Kotze,
- Sheena Kotze,
- Fatima Laher,
- Imre Laszlo,
- Erica Lazarus,
- Hua-Xin Liao,
- Yong Lin,
- Helen Lu,
- Judith Lucas,
- Mookho Malahleha,
- Tara McNair,
- Peter Meerts,
- Zinhle Mgaga,
- Mahlodi Montlha,
- Boitumelo Mosito,
- Andrew Moultrie,
- Sarah Mudrak,
- Valérie Oriol-Mathieu,
- Marcella Sarzotti-Kelsoe,
- Matson Tso Mathebula,
- Mitch Matoga,
- Rachael McClennen,
- Pamela Mda,
- Peter Meerts,
- Vimla Naicker,
- Logashvari Naidoo,
- Cindy-Ann Okkers,
- Saleha Omarjee,
- Hella Pasmans,
- Tricia Philip,
- Abraham Pinter,
- Annah Pitsi,
- Ornelia Ramos,
- April Randhawa,
- Sanne Roels,
- Shamiska Rohith,
- Lucy Rutten,
- Jerald Sadoff,
- Gabriela Salinas,
- Yvonne Salzgeber,
- Lorenz Scheppler,
- Katharine Schwedhelm,
- Nicolette Schuller,
- Angelina Sharak,
- Sherry Stanfield-Oakley,
- Carrie Sopher,
- Terence Tafatatha,
- Simbarashe G. Takuva,
- Chan Tang,
- An Vandebosch,
- Edna Viegas,
- Valentin Voillet,
- Frank Wegmann,
- Mo Weijtens,
- Stephany Wilcox,
- Anthony Williams,
- Chenchen Yu,
- Pei-Chun Yu,
- Olive Yuan,
- Xuehan Zhang
Affiliations
- Avi Kenny
- Department of Biostatistics, University of Washington, Seattle, WA, USA
- Janine van Duijn
- Janssen Vaccines & Prevention BV, Leiden, the Netherlands
- One Dintwe
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA; Cape Town HVTN Immunology Laboratory, Hutchinson Centre Research Institute of South Africa, Cape Town, South Africa
- Jack Heptinstall
- Center for Human Systems Immunology, Department of Surgery, Duke University, Durham, NC, USA; Duke Human Vaccine Institute, Durham, NC, USA
- Randy Burnham
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA
- Sheetal Sawant
- Center for Human Systems Immunology, Department of Surgery, Duke University, Durham, NC, USA; Duke Human Vaccine Institute, Durham, NC, USA
- Lu Zhang
- Center for Human Systems Immunology, Department of Surgery, Duke University, Durham, NC, USA; Duke Human Vaccine Institute, Durham, NC, USA
- Dieter Mielke
- Center for Human Systems Immunology, Department of Surgery, Duke University, Durham, NC, USA
- Sharon Khuzwayo
- Cape Town HVTN Immunology Laboratory, Hutchinson Centre Research Institute of South Africa, Cape Town, South Africa
- Faatima Laher Omar
- Cape Town HVTN Immunology Laboratory, Hutchinson Centre Research Institute of South Africa, Cape Town, South Africa
- Sherry Stanfield-Oakley
- Center for Human Systems Immunology, Department of Surgery, Duke University, Durham, NC, USA
- Taylor Keyes
- Center for Human Systems Immunology, Department of Surgery, Duke University, Durham, NC, USA
- Brooke Dunn
- Center for Human Systems Immunology, Department of Surgery, Duke University, Durham, NC, USA
- Derrick Goodman
- Center for Human Systems Immunology, Department of Surgery, Duke University, Durham, NC, USA; Duke Human Vaccine Institute, Durham, NC, USA
- Youyi Fong
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA; Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA
- David Benkeser
- Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, USA
- Rodger Zou
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA
- John Hural
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA
- Ollivier Hyrien
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA
- Michal Juraska
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA
- Alex Luedtke
- Department of Statistics, University of Washington, Seattle, WA, USA
- Lars van der Laan
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA; Department of Statistics, University of Washington, Seattle, WA, USA
- Elena E. Giorgi
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA
- Craig Magaret
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA
- Lindsay N. Carpp
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA
- Laura Pattacini
- Janssen Vaccines & Prevention BV, Leiden, the Netherlands
- Tom van de Kerkhof
- Janssen Vaccines & Prevention BV, Leiden, the Netherlands
- Bette Korber
- Los Alamos National Laboratory, Los Alamos, NM, USA; New Mexico Consortium, Los Alamos, NM, USA
- Wouter Willems
- Janssen Research & Development BE, Beerse, Belgium
- Leigh H. Fisher
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA
- Hanneke Schuitemaker
- Janssen Vaccines & Prevention BV, Leiden, the Netherlands
- Edith Swann
- Division of AIDS, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA
- James G. Kublin
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA
- Maria G. Pau
- Janssen Infectious Diseases BV, Beerse, Belgium
- Susan Buchbinder
- San Francisco Department of Public Health, San Francisco, CA, USA
- Frank Tomaka
- Janssen Research & Development, LLC, Titusville, NJ, USA
- Steven Nijs
- Janssen Infectious Diseases BV, Beerse, Belgium
- Ludo Lavreys
- Janssen Infectious Diseases BV, Beerse, Belgium
- Huub C. Gelderblom
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA
- Lawrence Corey
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA; Department of Medicine, University of Washington, Seattle, WA, 98195, USA
- Kathryn Mngadi
- The Aurum Institute, Johannesburg, South Africa
- Glenda E. Gray
- South African Medical Research Council, Cape Town, South Africa
- Erica Borducchi
- Center for Virology & Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Jenny Hendriks
- Janssen Vaccines & Prevention BV, Leiden, the Netherlands
- Kelly E. Seaton
- Center for Human Systems Immunology, Department of Surgery, Duke University, Durham, NC, USA; Duke Human Vaccine Institute, Durham, NC, USA
- Susan Zolla-Pazner
- Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Dan H. Barouch
- Center for Virology & Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Cambridge, MA, USA
- Guido Ferrari
- Center for Human Systems Immunology, Department of Surgery, Duke University, Durham, NC, USA; Duke Human Vaccine Institute, Durham, NC, USA
- Stephen C. De Rosa
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA
- M Juliana McElrath
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA
- Erica Andersen-Nissen
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA; Cape Town HVTN Immunology Laboratory, Hutchinson Centre Research Institute of South Africa, Cape Town, South Africa
- Daniel J. Stieh
- Janssen Vaccines & Prevention BV, Leiden, the Netherlands
- Georgia D. Tomaras
- Center for Human Systems Immunology, Department of Surgery, Duke University, Durham, NC, USA; Duke Human Vaccine Institute, Durham, NC, USA; Department of Integrative Immunobiology, Duke University, Durham, NC, USA; Corresponding author. Duke Center for Human Systems Immunology, Departments of Surgery, Immunology, Molecular Genetics and Microbiology, Duke University, Room 4079 MSRBII, 2 Genome Ct, Durham, NC, 27710, USA.
- Peter B. Gilbert
- Department of Biostatistics, University of Washington, Seattle, WA, USA; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA; Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA; Corresponding author. Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, 1100 Fairview Avenue North, M2-C200, Seattle, WA, 98109, USA.
- Jon Allagappen
- Jessica Andriesen
- Alison Ayres
- Saman Baral
- Linda-Gail Bekker
- Asiphe Besethi
- Caroline Borremans
- Esmee Braams
- Caroline Brackett
- William Brumskine
- Roma Chilengi
- Rachel Choi
- Thozama Dubula
- Jaiden Seongmi Dumas
- Brooke Dunn
- Radhika Etikala
- Zelda Euler
- Sarah Everett
- Nigel Garrett
- Huub Gelderblom
- Katherine Gill
- Kevin Gillespie
- Dimitri Goedhart
- Erik Goosmann
- Shannon Grant
- Ellie Hands
- Barton Haynes
- Bronwill Herringer
- Zaheer Hoosain
- Mina Hosseinipour
- Portia Hunidzarira
- Julia Hutter
- Mubiana Inambao
- Craig Innes
- Taylor Keyes
- William Kilembe
- Philippus Kotze
- Sheena Kotze
- Fatima Laher
- Imre Laszlo
- Erica Lazarus
- Hua-Xin Liao
- Yong Lin
- Helen Lu
- Judith Lucas
- Mookho Malahleha
- Tara McNair
- Peter Meerts
- Zinhle Mgaga
- Mahlodi Montlha
- Boitumelo Mosito
- Andrew Moultrie
- Sarah Mudrak
- Valérie Oriol-Mathieu
- Marcella Sarzotti-Kelsoe
- Matson Tso Mathebula
- Mitch Matoga
- Rachael McClennen
- Pamela Mda
- Peter Meerts
- Vimla Naicker
- Logashvari Naidoo
- Cindy-Ann Okkers
- Saleha Omarjee
- Hella Pasmans
- Tricia Philip
- Abraham Pinter
- Annah Pitsi
- Ornelia Ramos
- April Randhawa
- Sanne Roels
- Shamiska Rohith
- Lucy Rutten
- Jerald Sadoff
- Gabriela Salinas
- Yvonne Salzgeber
- Lorenz Scheppler
- Katharine Schwedhelm
- Nicolette Schuller
- Angelina Sharak
- Sherry Stanfield-Oakley
- Carrie Sopher
- Terence Tafatatha
- Simbarashe G. Takuva
- Chan Tang
- An Vandebosch
- Edna Viegas
- Valentin Voillet
- Frank Wegmann
- Mo Weijtens
- Stephany Wilcox
- Anthony Williams
- Chenchen Yu
- Pei-Chun Yu
- Olive Yuan
- Xuehan Zhang
- Journal volume & issue
-
Vol. 108
p. 105320
Abstract
Summary: Background: The HVTN 705 Imbokodo trial of 2636 people without HIV and assigned female sex at birth, conducted in southern Africa, evaluated a heterologous HIV-1 vaccine regimen: mosaic adenovirus 26-based vaccine (Ad26.Mos4.HIV) at Months 0, 3, 6, 12 and alum-adjuvanted clade C gp140 at Months 6, 12. Per-protocol vaccine efficacy (VE) against HIV-1 diagnosis from seven to 24 months was 14.1% (95% CI: −22.0% to 39.5%). Immune correlates analysis was performed for markers selected based on prior evidence in efficacy trials and/or nonhuman primate models. Methods: Humoral and cellular immune response markers at Month 7 were evaluated as immune correlates of risk and of protection in a breakthrough case–control cohort (n = 52 cases, 246 non-cases). Primary markers were IgG binding to vaccine-strain gp140, IgG3 binding to diverse Env antigens (IgG3 Env breadth), IgG3 binding to diverse V1V2 antigens (IgG3 V1V2 breadth), antibody-dependent phagocytosis against the vaccine-strain gp140, Env-specific CD4+ and CD8+ T-cell responses, and multi-epitope functions. Findings: No immune markers were statistically significant correlates of risk. IgG3 V1V2 breadth trended toward an inverse association: hazard ratio 0.70 (95% CI: 0.36 to 1.35; p = 0.29) per 10-fold increase and 0.51 (95% CI: 0.21 to 1.24; p = 0.14) in a Cox model with all primary markers. The VE estimate was 11.8% (95% CI: −17.9% to 34.0%) at all IgG3 V1V2 breadth values below 667 weighted geometric mean net MFI; just above this value, the VE estimate sharply increased to 62.6% (95% CI: −17.9% to 89.6%), and further increased to 80.9% (95% CI: −17.9% to 99.5%) at 1471 MFI, the 95th percentile of the marker distribution. Mediation analysis yielded a VE of 35.7% (95% CI: 15.0% to 51.3%) attributable to the vaccine's impact on this marker. Interpretation: The trend in association of greater IgG3 V1V2 antibody breadth with lower likelihood of HIV acquisition is consistent with the identification of antibodies against V1V2 as immune correlates in three other HIV vaccine efficacy trials and suggests that a greater emphasis should be placed on studying this region in the HIV-1 envelope as a vaccine immunogen. Funding: National Institute of Allergy and Infectious Diseases and Janssen Vaccines & Prevention BV.
