Induction of HIV‐specific antibody response and protection against vaginal SHIV transmission by intranasal immunization with inactivated SHIV‐capturing nanospheres in macaques

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Abstract
We have previously reported that concanavalin A‐immobilized polystyrene nanospheres (Con A‐NS) could efficiently capture HIV‐1 particles and that intranasal immunization with inactivated HIV‐1‐capturing nanospheres (HIV‐NS) induced vaginal anti‐HIV‐1 IgA antibody response in mice. In this study, to evaluate the protective effect of immunization, each three macaques was intranasally immunized with Con A‐NS or inactivated simian/human immunodeficiency virus KU‐2‐capturing nanospheres (SHIV‐NS) and then intravaginally challenged with a pathogenic virus, SHIV KU‐2. After a series of six immunizations, vaginal anti‐HIV‐1 gp120 IgA and IgG antibodies were detected in all SHIV‐NS‐immunized macaques. After intravaginal challenge, one of the three macaques in each of the Con A‐NS‐ and SHIV‐NS‐immunized groups was infected. Plasma viral RNA load of infected macaque in SHIV‐NS‐immunized macaques was substantially less than that in unimmunized control macaque and reached below the detectable level. However, it could not be determined whether intranasal immunization with SHIV‐NS is effective in giving complete protection against intravaginal challenge. To explore the effect of the SHIV‐NS vaccine, the remaining non‐infected macaques were rechallenged intravenously with SHIV KU‐2. After intravenous challenge, all macaques became infected. However, SHIV‐NS‐immunized macaques had lower viral RNA loads and higher CD4+ T cell counts than unimmunized control macaques. Plasma anti‐HIV‐1 gp120 IgA and IgG antibodies were induced more rapidly in the SHIV‐NS‐immunized macaques than in the controls. The rapid antibody responses having neutralizing activity might contribute to the clearance of the challenge virus. Thus, SHIV‐NS‐immunized macaques exhibited partial protection to vaginal and systemic challenges with SHIV KU‐2. J. Med. Virol. 73:368–377, 2004.

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