Immunogenicity and cross-reactivity of rhesus adenoviral vectors

Journal article

Adenovirus (Ad) vectors are being investigated as vaccine candidates, but baseline anti-vector immunity exists in human populations to both human Ad (HuAd) and chimpanzee Ad (ChAd) vectors. In this study, we investigated the immunogenicity and cross-reactivity of a panel of recently described rhesus adenoviral (RhAd) vectors. RhAd vectors elicited T cells with low exhaustion markers and robust anamnestic potential. Moreover, RhAd vector immunogenicity was unaffected by high levels of pre-existing anti-HuAd immunity. Both HuAd/RhAd and RhAd/RhAd prime-boost vaccine regimens were highly immunogenic, despite a degree of cross-reactive neutralizing antibodies (NAbs) between phylogenetically related RhAd vectors. We observed extensive vector-specific cross-reactive CD4 T cell responses and more limited CD8 T cell responses between RhAd and HuAd vectors, but the impact of vector-specific cellular responses was far less than vector-specific NAbs. These data suggest the potential utility of RhAd vectors and define novel heterologous prime-boost strategies for vaccine development.IMPORTANCE To date, most adenoviral vectors developed for vaccination have been HuAds from species B, C, D, and E and display moderate to high levels of pre-existing immunity in human populations. There is a clinical need for new adenoviral vectors that are not hindered by pre-existing immunity. Moreover, the development of RhAd vector vaccines expands our ability to vaccinate against multiple pathogens in a population that may have received other HuAd or ChAd vectors. We evaluated the immunogenicity and cross-reactivity of RhAd vectors, which belong to the poorly described adenovirus species G. These vectors induce robust cellular and humoral immune responses and were not hampered by pre-existing anti-HuAd vector immunity. Such properties make RhAd vectors attractive as potential vaccine vectors.

Authors: Iampietro, M; Larocca, R; Provine, N; Abbink, P; Kang, Z

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: American Society for Microbiology
• Journal: Journal of Virology
• Volume: 92
• Issue: 11
• Article number: e00159-18
• Publication date: 2018-03-21
• Acceptance date: 2018-03-13
• DOI: 10.1128/jvi.00159-18
• EISSN: 1098-5514
• ISSN: 0022-538X
• Pmid: 29563285
• Language: English
• Keywords: Journal Article