Humoral immunity induced by mucosal and/or systemic SIV-specific vaccine platforms suggests novel combinatorial approaches for enhancing responses.
Combinatorial HIV/SIV vaccine approaches targeting multiple arms of the immune system might improve protective efficacy. We compared SIV-specific humoral immunity induced in rhesus macaques by five vaccine regimens. Systemic regimens included ALVAC-SIVenv priming and Env boosting (ALVAC/Env); DNA immunization; and DNA plus Env co-immunization (DNA&Env). RepAd/Env combined mucosal replication-competent Ad-env priming with systemic Env boosting. A Peptide/Env regimen, given solely intrarectally, included HIV/SIV peptides followed by MVA-env and Env boosts. Serum antibodies mediating neutralizing, phagocytic and ADCC activities were induced by ALVAC/Env, RepAd/Env and DNA&Env vaccines. Memory B cells and plasma cells were maintained in the bone marrow. RepAd/Env vaccination induced early SIV-specific IgA in rectal secretions before Env boosting, although mucosal IgA and IgG responses were readily detected at necropsy in ALVAC/Env, RepAd/Env, DNA&Env and DNA vaccinated animals. Our results suggest that combined RepAd priming with ALVAC/Env or DNA&Env regimen boosting might induce potent, functional, long-lasting systemic and mucosal SIV-specific antibodies.
Vargas-Inchaustegui, DA; Tuero, I; Mohanram, V; Musich, T; Pegu, P; Valentin, A; Sui, Y; Rosati, M; Bear, J; Venzon, DJ; Kulkarni, V; Alicea, C; Pilkington, GR; Liyanage, NPM; Demberg, T; Gordon, SN; Wang, Y; Hogg, AE; Frey, B; Patterson, LJ; DiPasquale, J; Montefiori, DC; Sardesai, NY; Reed, SG; Berzofsky, JA; Franchini, G; Felber, BK; Pavlakis, GN; Robert-Guroff, M
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