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

Fouda, G. G.; Berendam, S. J.; Morgan-Asiedu, P. K.; Mangan, R. J.; Li, S.; Heimsath, H.; Luo, K.; Curtis, A. D.; Eudailey, J. A.; Fox, C. B.; Tomai, M. A.; Phillips, B.; Itell, H. L.; Kunz, E.; Hudgens, M.; Cronin, K.; Wiehe, K.; Alam, S. M.; Van Rompay, K. K. A.; De Paris, K.; Permar, S. R.; Moody, M. A.

doi:10.1101/2021.08.18.456876

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bioRxiv · 10.1101/2021.08.18.456876

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

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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 coadministered 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.

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Fouda, G. G., Berendam, S. J., Morgan-Asiedu, P. K., Mangan, R. J., Li, S., Heimsath, H., Luo, K., Curtis, A. D., Eudailey, J. A., Fox, C. B., Tomai, M. A., Phillips, B., Itell, H. L., Kunz, E., Hudgens, M., Cronin, K., Wiehe, K., Alam, S. M., Van Rompay, K. K. A., De Paris, K., Permar, S. R., Moody, M. A.. 2021-08-20. Different adjuvanted pediatric HIV envelope vaccines induced distinct plasma antibody responses despite similar B cell receptor repertoires in infant rhesus macaques.. https://doi.org/10.1101/2021.08.18.456876

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