Tonsillar Application of AT-2 SIV Affords Partial Protection Against Rectal Challenge With SIVmac239

Background: Although mucosal responses are important for preventing infections with HIV, the optimal strategies for inducing them remain unclear. To evaluate vaccine strategies targeting the oral mucosal lymphoid tissue inductive sites as an approach to provide immunity at distal sites, we vaccinated healthy macaques via the palatine/lingual tonsils with aldrithiol 2 (AT-2) inactivated Simian immunodeficiency virus (SIV)mac239, combined with CpG-C immunostimulatory oligonucleotide (CpG-C ISS-ODN, C274) as the adjuvant. Methods: Macaques received 5 doses of C274 or control ODN C661 and AT-2 SIV on the tonsillar tissues every 6 weeks before being challenged rectally with SIVmac239, 8 weeks after the last immunization. Results: Although no T-cell or B-cell responses were detected in the blood before challenge, antibody (Ab) responses were detected in the rectum. Immunization with AT-2 SIV significantly reduced the frequency of infection compared with nonimmunized controls, irrespective of adjuvant. In the vaccinated animals that became infected, peak viremias were somewhat reduced. SIV-specific responses were detected in the blood once animals became infected with no detectable differences between the differently immunized groups and the controls. Conclusion: This work provides evidence that vaccine immunogens applied to the oral mucosal associated lymphoid tissues can provide benefit against rectal challenge, a finding with important implications for mucosal vaccination strategies.

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