Immunogenicity of 2 therapeutic mosaic HIV-1 vaccine strategies in individuals with HIV-1 on antiretroviral therapy.
Journal
NPJ vaccines
ISSN: 2059-0105
Titre abrégé: NPJ Vaccines
Pays: England
ID NLM: 101699863
Informations de publication
Date de publication:
23 May 2024
23 May 2024
Historique:
received:
12
05
2023
accepted:
17
04
2024
medline:
24
5
2024
pubmed:
24
5
2024
entrez:
23
5
2024
Statut:
epublish
Résumé
Mosaic HIV-1 vaccines have been shown to elicit robust humoral and cellular immune responses in people living with HIV-1 (PLWH), that had started antiretroviral therapy (ART) during acute infection. We evaluated the safety and immunogenicity of 2 mosaic vaccine regimens in virologically suppressed individuals that had initiated ART during the chronic phase of infection, exemplifying the majority of PLWH. In this double-blind, placebo-controlled phase 1 trial (IPCAVD013/HTX1002) 25 ART-suppressed PLWH were randomized to receive Ad26.Mos4.HIV/MVA-Mosaic (Ad26/MVA) (n = 10) or Ad26.Mos4.HIV/Ad26.Mos4.HIV plus adjuvanted gp140 protein (Ad26/Ad26+gp140) (n = 9) or placebo (n = 6). Primary endpoints included safety and tolerability and secondary endpoints included HIV-specific binding and neutralizing antibody titers and HIV-specific T cell responses. Both vaccine regimens were well tolerated with pain/tenderness at the injection site and fatigue, myalgia/chills and headache as the most commonly reported solicited local and grade 3 systemic adverse events, respectively. In the Ad26/Ad26+gp140 group, Env-specific IFN-γ T cell responses showed a median 12-fold increase while responses to Gag and Pol increased 1.8 and 2.4-fold, respectively. The breadth of T cell responses to individual peptide subpools increased from 11.0 pre-vaccination to 26.0 in the Ad26/Ad26+gp140 group and from 10.0 to 14.5 in the Ad26/MVA group. Ad26/Ad26+gp140 vaccination increased binding antibody titers against vaccine-matched clade C Env 5.5-fold as well as augmented neutralizing antibody titers against Clade C pseudovirus by 7.2-fold. Both vaccine regimens were immunogenic, while the addition of the protein boost resulted in additional T cell and augmented binding and neutralizing antibody titers. These data suggest that the Ad26/Ad26+gp140 regimen should be tested further.
Identifiants
pubmed: 38782902
doi: 10.1038/s41541-024-00876-2
pii: 10.1038/s41541-024-00876-2
doi:
Types de publication
Journal Article
Langues
eng
Pagination
89Subventions
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)
ID : AI138790
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)
ID : AI149670
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)
ID : AI169615
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)
ID : AI128751
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)
ID : AI164556
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)
ID : AI177687
Organisme : Ragon Institute of MGH, MIT and Harvard (Ragon Institute)
ID : Internal grant
Informations de copyright
© 2024. The Author(s).
Références
Julg, B. & Barouch, D. H. Novel immunological strategies for HIV-1 eradication. J. Virus Erad. 1, 232–236 (2015).
doi: 10.1016/S2055-6640(20)30931-6
pubmed: 27482421
pmcid: 4946653
Chen, Z. & Julg, B. Therapeutic vaccines for the treatment of HIV. Transl. Res. 223, 61–75 (2020).
doi: 10.1016/j.trsl.2020.04.008
pubmed: 32438074
pmcid: 8188575
Barouch, D. H. et al. Evaluation of a mosaic HIV-1 vaccine in a multicentre, randomised, double-blind, placebo-controlled, phase 1/2a clinical trial (APPROACH) and in rhesus monkeys (NHP 13-19). Lancet 392, 232–243 (2018).
doi: 10.1016/S0140-6736(18)31364-3
pubmed: 30047376
pmcid: 6192527
Baden, L. R. et al. First-in-human randomized, controlled trial of mosaic HIV-1 immunogens delivered via a modified vaccinia ankara vector. J. Infect. Dis. 218, 633–644 (2018).
doi: 10.1093/infdis/jiy212
pubmed: 29669026
pmcid: 6047429
Borducchi, E. N. et al. Ad26/MVA therapeutic vaccination with TLR7 stimulation in SIV-infected rhesus monkeys. Nature 540, 284–287 (2016).
doi: 10.1038/nature20583
pubmed: 27841870
pmcid: 5145754
Colby, D. J. et al. Safety and immunogenicity of Ad26 and MVA vaccines in acutely treated HIV and effect on viral rebound after antiretroviral therapy interruption. Nat. Med. 26, 498–501 (2020).
doi: 10.1038/s41591-020-0774-y
pubmed: 32235883
Ackerman, M. E. et al. A robust, high-throughput assay to determine the phagocytic activity of clinical antibody samples. J. Immunol. Methods 366, 8–19 (2011).
doi: 10.1016/j.jim.2010.12.016
pubmed: 21192942
Crepaz, N., Song, R., Lyss, S. B. & Hall, H. I. Estimated time from HIV infection to diagnosis and diagnosis to first viral suppression during 2014-2018. AIDS 35, 2181–2190 (2021).
doi: 10.1097/QAD.0000000000003008
pubmed: 34172670
Okulicz, J. F. et al. Influence of the timing of antiretroviral therapy on the potential for normalization of immune status in human immunodeficiency virus 1-infected individuals. JAMA Intern. Med. 175, 88–99 (2015).
doi: 10.1001/jamainternmed.2014.4010
pubmed: 25419650
pmcid: 4286496
Trautmann, L. et al. Profound metabolic, functional, and cytolytic differences characterize HIV-specific CD8 T cells in primary and chronic HIV infection. Blood 120, 3466–3477 (2012).
doi: 10.1182/blood-2012-04-422550
pubmed: 22955926
pmcid: 3743465
Takata, H. et al. Long-term antiretroviral therapy initiated in acute HIV infection prevents residual dysfunction of HIV-specific CD8(+) T cells. EBioMedicine 84, 104253 (2022).
doi: 10.1016/j.ebiom.2022.104253
pubmed: 36088683
pmcid: 9471490
Moir, S. et al. B cells in early and chronic HIV infection: evidence for preservation of immune function associated with early initiation of antiretroviral therapy. Blood 116, 5571–5579 (2010).
doi: 10.1182/blood-2010-05-285528
pubmed: 20837780
pmcid: 3031405
Ventura, J. D. et al. Therapeutic efficacy of an Ad26/MVA vaccine with SIV gp140 protein and vesatolimod in ART-suppressed rhesus macaques. NPJ Vaccines 7, 53 (2022).
doi: 10.1038/s41541-022-00477-x
pubmed: 35585080
pmcid: 9117189
Zurawski, G. et al. Superiority in rhesus macaques of targeting HIV-1 Env gp140 to CD40 versus LOX-1 in combination with replication-competent NYVAC-KC for induction of env-specific antibody and T cell responses. J. Virol. 91, e01596-16 (2017).
Tsang, J. S. et al. Improving vaccine-induced immunity: can baseline predict outcome? Trends Immunol. 41, 457–465 (2020).
doi: 10.1016/j.it.2020.04.001
pubmed: 32340868
pmcid: 7142696
Tsang, J. S. et al. Global analyses of human immune variation reveal baseline predictors of postvaccination responses. Cell 157, 499–513 (2014).
doi: 10.1016/j.cell.2014.03.031
pubmed: 24725414
pmcid: 4139290
Radebe, M. et al. Broad and persistent Gag-specific CD8+ T-cell responses are associated with viral control but rarely drive viral escape during primary HIV-1 infection. AIDS 29, 23–33 (2015).
doi: 10.1097/QAD.0000000000000508
pubmed: 25387316
Chevalier, M. F. et al. HIV-1-specific interleukin-21+ CD4+ T cell responses contribute to durable viral control through the modulation of HIV-specific CD8+ T cell function. J. Virol. 85, 733–741 (2011).
doi: 10.1128/JVI.02030-10
pubmed: 21047960
Julg, B. et al. Enhanced anti-HIV functional activity associated with Gag-specific CD8 T-cell responses. J. Virol. 84, 5540–5549 (2010).
doi: 10.1128/JVI.02031-09
pubmed: 20335261
pmcid: 2876607
Stieh, D. J. et al. Safety and immunogenicity of Ad26-vectored HIV vaccine with mosaic immunogens and a novel mosaic envelope protein in HIV-uninfected adults: a phase 1/2a study. J. Infect. Dis. 85, 733–741 (2022).
Baden, L. R. et al. Safety and immunogenicity of two heterologous HIV vaccine regimens in healthy, HIV-uninfected adults (TRAVERSE): a randomised, parallel-group, placebo-controlled, double-blind, phase 1/2a study. Lancet HIV 7, e688–e698 (2020).
doi: 10.1016/S2352-3018(20)30229-0
pubmed: 33010242
pmcid: 7529856
Dugast, A. S. et al. Lack of protection following passive transfer of polyclonal highly functional low-dose non-neutralizing antibodies. PLoS ONE 9, e97229 (2014).
doi: 10.1371/journal.pone.0097229
pubmed: 24820481
pmcid: 4018276
Li, M. et al. Human immunodeficiency virus type 1 env clones from acute and early subtype B infections for standardized assessments of vaccine-elicited neutralizing antibodies. J. Virol. 79, 10108–10125 (2005).
doi: 10.1128/JVI.79.16.10108-10125.2005
pubmed: 16051804
pmcid: 1182643
Rademeyer, C. et al. Features of recently transmitted HIV-1 clade C viruses that impact antibody recognition: implications for active and passive immunization. PLoS Pathog. 12, e1005742 (2016).
doi: 10.1371/journal.ppat.1005742
pubmed: 27434311
pmcid: 4951126
Sprangers, M. C. et al. Quantifying adenovirus-neutralizing antibodies by luciferase transgene detection: addressing preexisting immunity to vaccine and gene therapy vectors. J. Clin. Microbiol. 41, 5046–5052 (2003).
doi: 10.1128/JCM.41.11.5046-5052.2003
pubmed: 14605137
pmcid: 262545
Stephenson, K. E. et al. Quantification of the epitope diversity of HIV-1-specific binding antibodies by peptide microarrays for global HIV-1 vaccine development. J. Immunol. Methods 416, 105–123 (2015).
doi: 10.1016/j.jim.2014.11.006
pubmed: 25445329
Li, F. et al. Peptide selection for human immunodeficiency virus type 1 CTL-based vaccine evaluation. Vaccine 24, 6893–6904 (2006).
doi: 10.1016/j.vaccine.2006.06.009
pubmed: 16890329