Protein-based, but not viral vector alone, HIV vaccine boosting drives an IgG1-biased polyfunctional humoral immune response

Fischinger, Stephanie; Shin, Sally; Boudreau, Carolyn M.; Ackerman, Margaret E.; Rerks-Ngarm, Supachai; Pitisuttithum, Punnee; Nitayaphan, Sorachai; Kim, Jerome H.; Robb, Merlin L.; Michael, Nelson L.; O’Connell, Robert J.; Vasan, Sandhya; Streeck, Hendrik; Alter, Galit

doi:10.1172/jci.insight.135057

Cited by 13 publications

(13 citation statements)

References 31 publications

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“…Furthermore, RV306 participants received ALVAC-HIV both as a prime and together with AIDSVAX B/E boosts. Previous work on the RV305 and RV306 trials suggests that ALVAC-HIV has minimal impact when included in the late boost ( 7 , 16 ), thus suggesting that the main contribution of ALVAC-HIV might be during the priming phase.…”

Section: Discussionmentioning

confidence: 99%

ALVAC-HIV and AIDSVAX B/E vaccination induce improved immune responses compared with AIDSVAX B/E vaccination alone

Costanzo,

Paquin-Proulx,

Schuetz

et al. 2023

JCI Insight

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The RV144 phase III vaccine trial demonstrated that ALVAC-HIV and AIDSVAX B/E administration over 6 months resulted in 31% efficacy in preventing HIV acquisition, while administration of AIDSVAX B/E alone in both VAX003 and VAX004 studies failed to show efficacy. In this study, we aimed to understand the impact of ALVAC-HIV on the development of cellular, humoral, and functional immune responses compared to the administration of AIDSVAX B/E alone. ALVAC-HIV in combination with 3 doses of AIDSVAX B/E significantly increased CD4 + HIV-specific T cell responses, polyfunctionality, and proliferation compared with 3 doses of AIDSVAX B/E alone. Additionally, Env-specific plasmablasts and A244-specific memory B cells were identified with a significantly higher magnitude in the group that received ALVAC-HIV. Subsequently, data revealed increased magnitude of plasma IgG binding to and avidity for HIV Env in participants who received ALVAC-HIV compared with 3 doses of AIDSVAX B/E alone. Lastly, levels of the Fc-mediated effector functions antibody-dependent cellular cytotoxicity, NK cell activation, and trogocytosis were significantly increased in participants who received ALVAC-HIV compared with those receiving AIDSVAX B/E alone. Taken together, these results suggest that ALVAC-HIV plays an essential role in developing cellular and humoral immune responses to protein-boosted regimens relative to protein alone.

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Section: Discussionmentioning

confidence: 99%

ALVAC-HIV and AIDSVAX B/E vaccination induce improved immune responses compared with AIDSVAX B/E vaccination alone

Costanzo,

Paquin-Proulx,

Schuetz

et al. 2023

JCI Insight

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“…Efforts to replicate RV144 vaccine-mediated protection in South Africa using a regimen analogous to the one used in the RV144 trial but with a vaccine regimen based on clade C HIV, the HVTN702 vaccine trial, failed to protect against HIV infection (66,67). Companion phase II safety and immunogenicity vaccine trials showed that levels of anti-Env Abs induced by the clade C based vaccine regimens were as high if not higher than the levels induced by the RV144 vaccine regimen (3,62,68,69). These Abs responses were tested using cells coated with monomeric rgp120 and thus, the immune monitoring strategy preferentially detected Abs to CD4i epitopes.…”

Section: Discussionmentioning

confidence: 99%

“…This is likely due to the target cell we used to measure these functions. Rgp120-coated cells have been used extensively as target cells in the investigation of AD functions and in immune monitoring of HIV vaccine trials ( 3 , 10 , 13 , 14 , 17 – 19 , 40 , 42 , 59 – 62 ). Interaction of Env with CD4 exposes conserved residues that are generally hidden in Env on productively infected cells.…”

Section: Discussionmentioning

confidence: 99%

Polyfunctional Fc Dependent Activity of Antibodies to Native Trimeric Envelope in HIV Elite Controllers

et al. 2020

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Kant et al. HIV Envelope-Specific Antibody-Dependent Responses in these assays. Elite controllers did differ from the other groups by having AD functions that were highly polyfunctional and highly correlated with each other. PCR measurement of HIV reservoir size showed that ADCC activity was higher in ECs and VCs with a reservoir size below the limit of detection compared to those having a measurable HIV reservoir size.

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“…Specifically, repeated protein boosting regimens, such as those used in the nonprotective VAX-003 trial, forced class-switching to IgG2 and IgG4, leading to less functional antibodies, 89,[157][158][159] in contrast to the elevated IgG3 levels observed in RV144 linked to increased effector functions induced by a canarypox-vectored prime and two protein boosts. 157 However, subsequent boosts of uninfected RV144 trial participants with either vector or the protein alone failed to recall IgG3 responses, although functional IgG1 responses were recalled by the protein boost alone, 160 highlighting differences between the composition of the primary immune responses and long-term boosts.…”

Section: Functional Features Of Vaccine-mediated Immunitymentioning

confidence: 99%

Building a better antibody through the Fc: advances and challenges in harnessing antibody Fc effector functions for antiviral protection

Gunn

Bai

2021

Human Vaccines & Immunotherapeutics

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Antibodies can provide antiviral protection through neutralization and recruitment of innate effector functions through the Fc domain. While neutralization has long been appreciated for its role in antibodymediated protection, a growing body of work indicates that the antibody Fc domain also significantly contributes to antiviral protection. Recruitment of innate immune cells such as natural killer cells, neutrophils, monocytes, macrophages, dendritic cells and the complement system by antibodies can lead to direct restriction of viral infection as well as promoting long-term antiviral immunity. Monoclonal antibody therapeutics against viruses are increasingly incorporating Fc-enhancing features to take advantage of the Fc domain, uncovering a surprising breadth of mechanisms through which antibodies can control viral infection. Here, we review the recent advances in our understanding of antibody-mediated innate immune effector functions in protection from viral infection and review the current approaches and challenges to effectively leverage innate immune cells via antibodies.

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Protein-based, but not viral vector alone, HIV vaccine boosting drives an IgG1-biased polyfunctional humoral immune response

Cited by 13 publications

References 31 publications

ALVAC-HIV and AIDSVAX B/E vaccination induce improved immune responses compared with AIDSVAX B/E vaccination alone

ALVAC-HIV and AIDSVAX B/E vaccination induce improved immune responses compared with AIDSVAX B/E vaccination alone

Polyfunctional Fc Dependent Activity of Antibodies to Native Trimeric Envelope in HIV Elite Controllers

Building a better antibody through the Fc: advances and challenges in harnessing antibody Fc effector functions for antiviral protection

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