Comparison of systemic and mucosal immunization with replicating Single cycle Adenoviruses

Area of Science:

• Immunology
• Vaccinology
• Virology

Background:

• HIV-1 infection targets mucosal surfaces, necessitating vaccines that provide barrier protection and systemic immunity.
• Current HIV vaccines primarily use intramuscular (IM) delivery, but mucosal immunization may offer superior mucosal barrier responses.
• Single-cycle adenovirus (SC Ad) vectors are being explored for HIV vaccine development.

Purpose of the Study:

• To compare the immunogenicity of SC Ad HIV-1 Env vaccines delivered via IM, intranasal (IN), and intravaginal (IVAG) routes.
• To evaluate the impact of prime-boost strategies using different immunization routes.
• To assess the durability of immune responses elicited by mucosal versus systemic vaccination.

Main Methods:

• Mice and Syrian hamsters were immunized with SC Ad HIV-1 Env vaccines using IM, IN, or IVAG routes.
• Different prime-boost regimens were employed, varying the routes for initial priming and subsequent boosting.
• Antibody responses against HIV Env were measured after single immunization and boost.
• Antibody persistence was evaluated up to one year post-immunization.

Main Results:

• A single IN immunization with SC Ad HIV-1 Env vaccine elicited significant Env antibodies in mice, unlike IM or IVAG routes.
• Both IM and IN priming generated strong antibody responses upon boosting, irrespective of the boosting route.
• IVAG priming failed to induce robust antibody responses, even after boosting.
• In Syrian hamsters, IN immunization was the sole route to achieve significant Env antibodies after one dose.
• IN-primed animals showed higher antibody responses than IM-primed animals after IN or IM boosting.
• Antibodies persisted for one year only in animals receiving at least one IN mucosal immunization.

Conclusions:

• Intranasal immunization may be a superior priming strategy for HIV vaccines compared to IM or IVAG routes.
• Mucosal vaccination, specifically IN, demonstrates potential for inducing robust and durable antibody responses against HIV Env.
• Educating the immune system at mucosal sites early in vaccination may be beneficial for controlling HIV spread.