Vaccine induction of antibodies and tissue-resident CD8+ T cells enhances protection against mucosal SHIV-infection in young macaques

Petitdemange, Caroline; Kasturi, Sudhir Pai; Kozlowski, Pamela A.; Nabi, Rafiq; Quarnstrom, Clare F.; Reddy, Pradeep B. J.; Derdeyn, Cynthia A.; Spicer, Lori M.; Patel, Parin J.; Legere, Traci; Kovalenkov, Yevgeniy; LaBranche, Celia C.; Villinger, François; Tomai, Mark A.; Vasilakos, John P.; Haynes, Barton F.; Kang, C. Yong; Gibbs, James S.; Yewdell, Jonathan W.; Barouch, Dan H.; Wrammert, Jens; Montefiori, David C.; Hunter, Eric; Amara, Rama Rao; Masopust, David; Pulendran, Bali

doi:10.1172/jci.insight.126047

Cited by 51 publications

(63 citation statements)

References 71 publications

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“…Forty-five female rhesus macaques (Supplementary Table 1) were distributed into three groups of 15 animals each. Animals in group 1 received four consecutive immunizations of BG505 SOSIP.664 adjuvanted with the TLR7/8 ligand 3M-052 encapsulated in PLGA nanoparticles (SOSIP/3M-052) 22 . Animals in group 2 were vaccinated via a sequential regimen involving HVVs comprising VSV, VV and Ad5-expressing SIVmac239 Gag in concert with SOSIP/3M-052 administered at the corresponding time points used in group 1 (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Such mucosal-homing CD8 + tissue-resident memory T cells (TRMs) can be elicited by sequential immunization with heterologous vectors expressing the same antigen 20,21 . We recently showed that vaccination of macaques sequentially with three heterologous viral vectors (HVVs) expressing SIVmac239 Gag (vesicular stomatitis virus (VSV)-Gag, vaccinia virus (VV)-Gag and Ad5-Gag) induced a high magnitude of Gag-specific CD8 + effector T cell and TRM responses 22 . In this study, although CD8 + T cell responses alone were insufficient for protection against mucosal SHIV challenge, there was limited protection in younger animals when CD8 + T cell responses were combined with Env-specific binding antibody responses 22 .…”

Section: T Cell-inducing Vaccine Durably Prevents Mucosal Shiv Infectmentioning

confidence: 99%

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T cell-inducing vaccine durably prevents mucosal SHIV infection even with lower neutralizing antibody titers

Arunachalam

Charles²,

Joag

et al. 2020

Nat Med

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130

128

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Recent efforts toward an HIV vaccine focus on inducing broadly neutralizing antibodies, but eliciting both neutralizing antibodies (nAbs) and cellular responses may be superior. Here, we immunized macaques with an HIV envelope trimer, either alone to induce nAbs, or together with a heterologous viral vector regimen to elicit nAbs and cellular immunity, including CD8 + tissue-resident memory T cells. After ten vaginal challenges with autologous virus, protection was observed in both vaccine groups at 53.3% and 66.7%, respectively. A nAb titer >300 was generally associated with protection but in the heterologous viral vector + nAb group, titers <300 were sufficient. In this group, protection was durable as the animals resisted six more challenges 5 months later. Antigen stimulation of T cells in ex vivo vaginal tissue cultures triggered antiviral responses in myeloid and CD4 + T cells. We propose that cellular immune responses reduce the threshold of nAbs required to confer superior and durable protection.

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Section: Resultsmentioning

confidence: 99%

Section: T Cell-inducing Vaccine Durably Prevents Mucosal Shiv Infectmentioning

confidence: 99%

T cell-inducing vaccine durably prevents mucosal SHIV infection even with lower neutralizing antibody titers

Arunachalam

Charles²,

Joag

et al. 2020

Nat Med

Self Cite

130

128

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“…ALFA is believed to be an improvement to the highly successful but proprietary AS04 adjuvant, which contains free MPLA adsorbed to alum, and neither of these have been assessed for vaccination against HIV-1. Protection was determined by limiting-dose serial intrarectal challenge with the heterologous, tier 2, CCR5-tropic subtype C SHIV-1157ipd3N4 virus strain, considered to be a stringent model with limited vaccine efficacy achieved to date [20][21][22]. Adjuvanting with ALFA, but not alum, dramatically reduced the per-exposure infection risk, however, protection was limited to male animals.…”

Section: Introductionmentioning

confidence: 99%

Adjuvanted HIV-1 vaccine promotes antibody-dependent phagocytic responses and protects against heterologous SHIV challenge

Paquin‐Proulx

Montero

et al. 2020

PLoS Pathog

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To augment HIV-1 pox-protein vaccine immunogenicity using a next generation adjuvant, a prime-boost strategy of recombinant modified vaccinia virus Ankara and multimeric Env gp145 was evaluated in macaques with either aluminum (alum) or a novel liposomal monophosphoryl lipid A (MPLA) formulation adsorbed to alum, ALFA. Binding antibody responses were robust and comparable between arms, while antibody-dependent neutrophil and monocyte phagocytotic responses were greatly enhanced by ALFA. Per-exposure vaccine efficacy against heterologous tier 2 SHIV mucosal challenge was 90% in ALFA-adjuvanted males (P = 0.002), while alum conferred no protection. Half of the ALFA-adjuvanted males remained uninfected after the full challenge series, which spanned seven months after the last vaccination. Antibody-dependent monocyte and neutrophil phagocytic responses both strongly correlated with protection. Significant sex differences in infection risk were observed, with much lower infection rates in females than males. In humans, MPLA-liposome-alum adjuvanted gp120 also increased HIV-1-specific phagocytic responses relative to alum. Thus, next-generation liposome-based adjuvants can drive vaccine elicited

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“…Previous work by Pulendran has shown that encapsulation of Toll‐like receptor ligands and antigens in poly‐lactic‐co‐glycolic acid nanoparticles could produce robust and durable immune responses in mice and macaques . Pulendran showed a vaccination strategy that induces a high magnitude of HIV envelope‐specific antibody as well tissue‐resident memory T cells, resulting in enhanced protection against mucosal challenge with simian‐human immune deficiency virus in macaques …”

Section: Understanding Correlates Of Efficacy Using Systems Vaccinologymentioning

confidence: 99%

“…15 Pulendran showed a vaccination strategy that induces a high magnitude of HIV envelopespecific antibody as well tissue-resident memory T cells, resulting in enhanced protection against mucosal challenge with simian-human immune deficiency virus in macaques. 16…”

Section: Understanding Correlates Of Efficacy Using Systems Vaccinologymentioning

confidence: 99%

Vaccine innovations for emerging infectious diseases—a symposium report

Cable¹,

Srikantiah

Crowe

et al. 2019

Annals of the New York Academy of Sciences

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Vaccines have been incredibly successful at stemming the morbidity and mortality of infectious diseases worldwide. However, there are still no effective vaccines for many serious and potentially preventable infectious diseases. Advances in vaccine technology, including new delivery methods and adjuvants, as well as progress in systems biology and an increased understanding of the human immune system, hold the potential to address these issues. In addition, maternal immunization has opened an avenue to address infectious diseases in neonates and very young infants. This report summarizes the presentations from a 1‐day symposium at the New York Academy of Sciences entitled “Innovative Vaccines against Resistant Infectious Diseases and Emerging Threats,” held on May 20, 2019.

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Vaccine induction of antibodies and tissue-resident CD8+ T cells enhances protection against mucosal SHIV-infection in young macaques

Cited by 51 publications

References 71 publications

T cell-inducing vaccine durably prevents mucosal SHIV infection even with lower neutralizing antibody titers

T cell-inducing vaccine durably prevents mucosal SHIV infection even with lower neutralizing antibody titers

Adjuvanted HIV-1 vaccine promotes antibody-dependent phagocytic responses and protects against heterologous SHIV challenge

Vaccine innovations for emerging infectious diseases—a symposium report

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