Characterization of Humoral and Cellular Immune Responses Elicited by a Recombinant Adenovirus Serotype 26 HIV-1 Env Vaccine in Healthy Adults (IPCAVD 001)

ABSTRACT The high prevalence of preexisting immunity to adenovirus serotype 5 (Ad5) in human populations will likely limit the immunogenicity and clinical utility of recombinant Ad5 (rAd5) vector-based vaccines for human immunodeficiency virus type 1 and other pathogens. A potential solution to this problem is to utilize rAd vaccine vectors derived from rare Ad serotypes such as Ad35 and Ad11. We have previously reported that rAd35 vectors were immunogenic in the presence of anti-Ad5 immunity, but the immunogenicity of heterologous rAd prime-boost regimens and the extent that cross-reactive anti-vector immunity may limit this approach have not been fully explored. Here we assess the immunogenicity of heterologous vaccine regimens involving rAd5, rAd35, and novel rAd11 vectors expressing simian immunodeficiency virus Gag in mice both with and without anti-Ad5 immunity. Heterologous rAd prime-boost regimens proved significantly more immunogenic than homologous regimens, as expected. Importantly, all regimens that included rAd5 were markedly suppressed by anti-Ad5 immunity. In contrast, rAd35-rAd11 and rAd11-rAd35 regimens elicited high-frequency immune responses both in the presence and in the absence of anti-Ad5 immunity, although we also detected clear cross-reactive Ad35/Ad11-specific humoral and cellular immune responses. Nevertheless, these data suggest the potential utility of heterologous rAd prime-boost vaccine regimens using vectors derived from rare human Ad serotypes.

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Erratum to “Cross-subtype antibody and cellular immune responses induced by a polyvalent DNA prime–protein boost HIV-1 vaccine in healthy human volunteers” [Vaccine 26 (2008) 1098–1110]

Vaccine ◽

10.1016/j.vaccine.2008.04.025 ◽

2008 ◽

Vol 26 (31) ◽

pp. 3946

Keyword(s):

Immune Responses ◽

Healthy Human ◽

Cellular Immune Responses ◽

Protein Boost ◽

Human Volunteers ◽

Cellular Immune ◽

Hiv 1

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Cellular Immune Responses to Four Doses of Percutaneous Bacille Calmette-Guerin in Healthy Adults

The Journal of Infectious Diseases ◽

10.1086/515614 ◽

1998 ◽

Vol 178 (1) ◽

pp. 138-146 ◽

Cited By ~ 16

Author(s):

P. W. Lowry ◽

T. S. Ludwig ◽

J. A. Adams ◽

M. L. Fitzpatrick ◽

S. M. Grant ◽

...

Keyword(s):

Immune Responses ◽

Healthy Adults ◽

Bacille Calmette Guerin ◽

Cellular Immune Responses ◽

Cellular Immune

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Safety and Immunogenicity of Heterologous and Homologous 2-Dose Regimens of Adenovirus Serotype 26– and Modified Vaccinia Ankara–Vectored Ebola Vaccines: A Randomized, Controlled Phase 1 Study

The Journal of Infectious Diseases ◽

10.1093/infdis/jiaa586 ◽

2020 ◽

Cited By ~ 1

Author(s):

Neil Goldstein ◽

Viki Bockstal ◽

Stephan Bart ◽

Kerstin Luhn ◽

Cynthia Robinson ◽

...

Keyword(s):

Immune Responses ◽

Neutralizing Antibodies ◽

Ebola Virus ◽

Phase 1 ◽

Booster Vaccination ◽

Controlled Study ◽

Adenovirus Serotype ◽

Cellular Immune Responses ◽

High Doses ◽

Cellular Immune

Abstract Background This phase 1 placebo-controlled study assessed the safety and immunogenicity of 2-dose regimens of Ad26.ZEBOV (adenovirus serotype 26 [Ad26]) and MVA-BN-Filo (modified vaccinia Ankara [MVA]) vaccines with booster vaccination at day 360. Methods Healthy US adults (N = 164) randomized into 10 groups received saline placebo or standard or high doses of Ad26 or MVA in 2-dose regimens at 7-, 14-, 28-, or 56-day intervals; 8 groups received booster Ad26 or MVA vaccinations on day 360. Participants reported solicited and unsolicited reactogenicity; we measured immunoglobulin G binding, neutralizing antibodies and cellular immune responses to Ebola virus glycoprotein. Results All regimens were well tolerated with no serious vaccine-related adverse events. Heterologous (Ad26,MVA [dose 1, dose 2] or MVA,Ad26) and homologous (Ad26,Ad26) regimens induced humoral and cellular immune responses 21 days after dose 2; responses were higher after heterologous regimens. Booster vaccination elicited anamnestic responses in all participants. Conclusions Both heterologous and homologous Ad26,MVA Ebola vaccine regimens are well tolerated in healthy adults, regardless of interval or dose level. Heterologous 2-dose Ad26,MVA regimens containing an Ebola virus insert induce strong, durable humoral and cellular immune responses. Immunological memory was rapidly recalled by booster vaccination, suggesting that Ad26 booster doses could be considered for individuals at risk of Ebola infection, who previously received the 2-dose regimen.

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