Replication deficient human adenovirus vector serotype 19a/64: Immunogenicity in mice and female cynomolgus macaques

Area of Science:

• Immunology
• Vaccinology
• Viral Vector Technology

Background:

• Human adenovirus type 5 (hAd5) is a well-characterized vaccine vector.
• Human adenovirus type 19a/64 (hAd19a) is a rare serotype with efficient transduction of dendritic cells and muscle cells.
• Papillomavirus (PV) antigens are targets for vaccine development.

Purpose of the Study:

• To evaluate replication-deficient hAd19a and hAd5 vectors expressing a PV antigen fused to the human MHC class II associated invariant chain T cell adjuvant (hIi).
• To compare the immunogenicity of hAd19a and hAd5 vectors in mice and cynomolgus macaques.
• To assess the potential of hAd19a as an alternative vaccine vector to hAd5.

Main Methods:

• Designed replication-deficient hAd19a, hAd5, and modified vaccinia Ankara (MVA) vectors.
• Vectors expressed a papillomavirus (PV) antigen fused to the human MHC class II associated invariant chain T cell adjuvant (hIi).
• Investigated immunogenicity in vivo in mice (assessing T cell responses and impact of pre-existing Ad5 immunity) and cynomolgus macaques (evaluating CD8+ and CD4+ T cell responses after MVA boost).

Main Results:

• hAd5 vectors encoding hIi enhanced PV-specific CD8+ T cell responses in mice.
• hAd19a vaccination induced T cell responses comparable to hAd5 vaccination in mice.
• hAd19a-induced responses were not diminished by pre-existing Ad5 immunity in mice.
• In macaques, both hAd19a and hAd5 were equally potent in inducing CD8+ T cells post-MVA boost.
• hAd19a priming resulted in broader CD4+ T cell responses in macaques.

Conclusions:

• hAd19a demonstrates potential as a vaccine vector alternative to hAd5.
• hAd19a elicits potent T cell responses against PV antigens.
• The efficacy of hAd19a is not compromised by pre-existing Ad5 immunity.