Different adjuvanted pediatric HIV envelope vaccines induced distinct plasma antibody responses despite similar B cell receptor repertoires in infant rhesus macaques.

Stella J Berendam,Kristina De Paris,M Anthony Moody,Holly Heimsath,Sallie R Permar,Shuk Hang Li,Kevin Wiehe,Koen K A Van Rompay,Hannah L Itell,Mark A Tomai,S Munir Alam,Genevieve G Fouda,Riley J Mangan,Kan Luo,Joshua Eudailey ,Papa K Morgan-Asiedu ,Erika L Kunz ,Kenneth Cronin ,Bonnie Phillips ,Alan D Curtis ,Christopher B Fox ,Michael G Hudgens

doi:10.1371/journal.pone.0256885

Abstract

Different HIV vaccine regimens elicit distinct plasma antibody responses in both human and nonhuman primate models. Previous studies in human and non-human primate infants showed that adjuvants influenced the quality of plasma antibody responses induced by pediatric HIV envelope vaccine regimens. We recently reported that use of the 3M052-SE adjuvant and longer intervals between vaccinations are associated with higher magnitude of antibody responses in infant rhesus macaques. However, the impact of different adjuvants in HIV vaccine regimens on the developing infant B cell receptor (BCR) repertoire has not been studied. This study evaluated whether pediatric HIV envelope vaccine regimens with different adjuvants induced distinct antigen-specific memory B cell repertoires and whether specific immunoglobulin (Ig) immunogenetic characteristics are associated with higher magnitude of plasma antibody responses in vaccinated infant rhesus macaques. We utilized archived preclinical pediatric HIV vaccine studies PBMCs and tissue samples from 19 infant rhesus macaques immunized either with (i) HIV Env protein with a squalene adjuvant, (ii) MVA-HIV and Env protein co-administered using a 3-week interval, (iii) MVA-HIV prime/ protein boost with an extended 6-week interval between immunizations, or (iv) with HIV Env administered with 3M-052-SE adjuvant. Frequencies of vaccine-elicited HIV Env-specific memory B cells from PBMCs and tissues were similar across vaccination groups (frequency range of 0.06-1.72%). There was no association between vaccine-elicited antigen-specific memory B cell frequencies and plasma antibody titer or avidity. Moreover, the epitope specificity and Ig immunogenetic features of vaccine-elicited monoclonal antibodies did not differ between the different vaccine regimens. These data suggest that pediatric HIV envelope vaccine candidates with different adjuvants that previously induced higher magnitude and quality of plasma antibody responses in infant rhesus macaques were not driven by distinct antigen-specific memory BCR repertoires.

Highlights

In 2019, 85% of the estimated 1.3 million pregnant women living with HIV-1 globally received antiretroviral drugs to prevent transmission to their children [1]
Our results indicated that while the magnitude and quality of plasma antibody responses induced by pediatric HIV vaccine regimens with different adjuvants, the B cell repertoire profiles were not distinct between different vaccine regimens in infant rhesus macaques
We observed that while the peak immunogenicity across different vaccine groups was comparable the magnitude and quality of vaccine-induced HIV Env-specific responses was enhanced by increasing the timing of vaccination interval from 3 to 6 weeks [25] and by using the Toll-like receptor 7 and 8 (TLR7/8) agonist adjuvant 3M-052-SE when compared to alum or to the TLR4 ligand glucopyranosyl lipid formulated in SE (GLA-SE) [26]

Summary

Introduction

In 2019, 85% of the estimated 1.3 million pregnant women living with HIV-1 globally received antiretroviral drugs to prevent transmission to their children [1]. Non-neutralizing IgG that targeted the HIV-1 Env variable loops 1 and 2 (V1V2) were identified as correlates of protection from the RV144 study; HIV-1 Env-specific IgA plasma antibodies were associated with lack of protection [15] This finding reinvigorated the optimism that an effective HIV-1 vaccine is attainable. A phase 2b/3 study (HVTN 702 or Uhambo) in South Africa, which used a pox vector prime-protein boost vaccine regimen similar to RV144, albeit with distinct vaccine strains and a different adjuvant, did not reproduce the results from the RV144 study and showed no efficacy [16] These studies demonstrated that HIV-1 vaccine immunogens could induce robust levels of V1V2 IgG antibodies as well as polyfunctional CD4+ T cell responses as surrogate of possible protection [15, 17]

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