Innate immune signatures to a partially-efficacious HIV vaccine predict correlates of HIV-1 infection risk

Abstract

The pox-protein regimen tested in the RV144 trial is the only vaccine strategy demonstrated to prevent HIV-1 infection. Subsequent analyses identified antibody and cellular immune responses as correlates of risk (CoRs) for HIV infection. Early predictors of these CoRs could provide insight into vaccine-induced protection and guide efforts to enhance vaccine efficacy. Using specimens from a phase 1b trial of the RV144 regimen in HIV-1-uninfected South Africans (HVTN 097), we profiled innate responses to the first ALVAC-HIV immunization. PBMC transcriptional responses peaked 1 day post-vaccination. Type I and II interferon signaling pathways were activated, as were innate pathways critical for adaptive immune priming. We then identified two innate immune transcriptional signatures strongly associated with adaptive immune CoR after completion of the 4-dose regimen. Day 1 signatures were positively associated with antibody-dependent cellular cytotoxicity and phagocytosis activity at Month 6.5. Conversely, a signature present on Days 3 and 7 was inversely associated with Env-specific CD4+ T cell responses at Months 6.5 and 12; rapid resolution of this signature was associated with higher Env-specific CD4+ T-cell responses. These are the first-reported early immune biomarkers of vaccine-induced responses associated with HIV-1 acquisition risk in humans and suggest hypotheses to improve HIV-1 vaccine regimens.

Systemic IL-15, IFN-γ, and IP-10/CXCL10 signature associated with effective immune response to SARS-CoV-2 in BNT162b2 mRNA vaccine recipients

“…Identification of a robust signature of cytokine induction leading to successful vaccination would be important for further vaccine development and optimization (Arunachalam et al, 2020;Fourati et al, 2019;Hagan and Pulendran, 2018;Kuri-Cervantes et al, 2016). Immune signatures in vaccine recipients receiving yellow fever, HIV-Ade5, or HIV canary pox virus vaccine (ALVAC) vaccines have been described (Andersen-Nissen et al, 2021;Gaucher et al, 2008;Querec et al, 2009;Zak et al, 2012).…”

A Saccharomyces cerevisiae Fermentation Product (Olimond BB) Alters the Early Response after Influenza Vaccination in Racehorses

“…Therefore, although we did not determine serum cytokine concentrations, the observed changes in blood leukocyte composition are most likely not due to high concentrations of vaccination-induced inflammatory cytokines (e.g., IL-1β, IL-6, TNF). The effects reported in the racehorses may be due to a low level induction of cytokines, chemokines and other mediators, as observed after vaccination of humans against influenza [30] and more recently when analyzing the innate immune transcriptional signatures of peripheral blood mononuclear cells (PBMC) one day after vaccination of humans [31,32].…”

Contribution to HIV Prevention and Treatment by Antibody-Mediated Effector Function and Advances in Broadly Neutralizing Antibody Delivery by Vectored Immunoprophylaxis

“…Analysis of the elicited antibodies also found that ADCC by NK cells was a major correlate of protection in the monkeys. More recent studies investigating the correlates of protection in a phase 1B trial attempting to replicate the RV144 regimen in South Africa (HVTN 097) found that innate immune pathways were highly upregulated, including signatures of ADCC and ADCP however it failed to demonstrate significant protection ( 53 ). Collectively, these findings suggest antibodies capable of driving Fc-mediated effector functions may hold promise in future interventions designed to prevent HIV transmission.…”