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Transient viral exposure drives functionally-coordinated humoral immune responses in HIV-1 post-treatment controllers.

ABSTRACT: HIV-1 post-treatment controllers are rare individuals controlling HIV-1 infection for years after antiretroviral therapy interruption. Identification of immune correlates of control in post-treatment controllers could aid in designing effective HIV-1 vaccine and remission strategies. Here, we perform comprehensive immunoprofiling of the humoral response to HIV-1 in long-term post-treatment controllers. Global multivariate analyses combining clinico-virological and humoral immune data reveal distinct profiles in post-treatment controllers experiencing transient viremic episodes off therapy compared to those stably aviremic. Virally-exposed post-treatment controllers display stronger HIV-1 humoral responses, and develop more frequently Env-specific memory B cells and cross-neutralizing antibodies. Both are linked to short viremic exposures, which are also accompanied by an increase in blood atypical memory B cells and activated subsets of circulating follicular helper T cells. Still, most humoral immune variables only correlate with Th2-like circulating follicular helper T cells. Thus, post-treatment controllers form a heterogeneous group with two distinct viral behaviours and associated immune signatures. Post-treatment controllers stably aviremic present "silent" humoral profiles, while those virally-exposed develop functionally robust HIV-specific B-cell and antibody responses, which may participate in controlling infection.

SUBMITTER: Molinos-Albert LM

PROVIDER: S-EPMC9001681 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Transient viral exposure drives functionally-coordinated humoral immune responses in HIV-1 post-treatment controllers.

Molinos-Albert Luis M LM Lorin Valérie V Monceaux Valérie V Orr Sylvie S Essat Asma A Dufloo Jérémy J Schwartz Olivier O Rouzioux Christine C Meyer Laurence L Hocqueloux Laurent L Sáez-Cirión Asier A Mouquet Hugo H

Nature communications 20220411 1

HIV-1 post-treatment controllers are rare individuals controlling HIV-1 infection for years after antiretroviral therapy interruption. Identification of immune correlates of control in post-treatment controllers could aid in designing effective HIV-1 vaccine and remission strategies. Here, we perform comprehensive immunoprofiling of the humoral response to HIV-1 in long-term post-treatment controllers. Global multivariate analyses combining clinico-virological and humoral immune data reveal dist ...[more]

PMID: 35410989

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Project description:The coronavirus disease 2019 (COVID-19) pandemic has highlighted the need for safe and effective vaccines to be rapidly developed and distributed worldwide, especially considering the emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. Protein subunit vaccines have emerged as a promising approach due to their proven safety record and ability to elicit robust immune responses. In this study, we evaluated the immunogenicity and efficacy of an adjuvanted tetravalent S1 subunit protein COVID-19 vaccine candidate composed of the Wuhan, B.1.1.7 variant, B.1.351 variant, and P.1 variant spike proteins in a nonhuman primate model with controlled SIVsab infection. The vaccine candidate induced both humoral and cellular immune responses, with T and B cell responses mainly peaking post boost immunization. The vaccine also elicited neutralizing and cross-reactive antibodies, angiotensin-converting enzyme 2 (ACE2)-blocking antibodies, and T cell responses, including spike-specific CD4+ T cells. Importantly, the vaccine candidate was able to generate Omicron variant spike-binding and ACE2-blocking antibodies without specifically vaccinating with Omicron, suggesting potential broad protection against emerging variants. The tetravalent composition of the vaccine candidate has significant implications for COVID-19 vaccine development and implementation, providing broad antibody responses against numerous SARS-CoV-2 variants. IMPORTANCE The study provides important insights into the immunogenicity and efficacy of a tetravalent protein subunit vaccine candidate against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The vaccine induced both humoral and cellular immune responses in nonhuman primates with controlled SIVagm infection and was able to generate Omicron variant-specific antibodies without specifically vaccinating with Omicron. These findings suggest that the tetravalent composition of the vaccine candidate could provide broad protection against multiple SARS-CoV-2 variants while minimizing the risk of immune escape and the emergence of new variants. Additionally, the use of rhesus macaques with controlled SIVsab infection may better represent vaccine immunogenicity in humans with chronic viral diseases, highlighting the importance of preclinical animal models in vaccine development. Overall, the study provides valuable information for the development and implementation of coronavirus disease 2019 vaccines, particularly for achieving global vaccine equity and addressing emerging variants.

Dataset Information

Transient viral exposure drives functionally-coordinated humoral immune responses in HIV-1 post-treatment controllers.

Publications

Transient viral exposure drives functionally-coordinated humoral immune responses in HIV-1 post-treatment controllers.

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