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Utilizing the Antigen Capsid-Incorporation Strategy for the Development of Adenovirus Serotype 5-Vectored Vaccine Approaches
Published on: May 6, 2015
Efficacy of multivalent adenovirus-based vaccine against simian immunodeficiency virus challenge
Danilo R Casimiro1, Kara Cox, Aimin Tang
1Department of Vaccines Basic Research, Merck Research Laboratories, Merck & Co., West Point, Pennsylvania 19486, USA. danilo_casimiro@merck.com
Abstract:
The prophylactic efficacies of several multivalent replication-incompetent adenovirus serotype 5 (Ad5) vaccines were examined in rhesus macaques using an intrarectal high-dose simian immunodeficiency virus SIVmac239 challenge model. Cohorts of Mamu-A*01(+)/B*17(-) Indian rhesus macaques were immunized with one of several combinations of Ad5 vectors expressing Gag, Pol, Nef, and Env gp140; for comparison, a Mamu-A*01(+) cohort was immunized using the Ad5 vector alone. There was no sign of immunological interference between antigens in the immunized animals. In general, expansion of the antigen breadth resulted in more favorable virological outcomes. In particular, the order of efficacy trended as follows: Gag/Pol/Nef/Env approximately Gag/Pol > Gag approximately Gag/Pol/Nef > Nef. However, the precision in ranking the vaccines based on the study results may be limited by the cohort size, and as such, may warrant additional testing. The implications of these results in light of the recent discouraging results of the phase IIb study of the trivalent Ad5 HIV-1 vaccine are discussed.
Insights
Multivalent adenovirus type 5 (Ad5) vaccines expressing SIV antigens showed prophylactic efficacy in rhesus macaques. Broader antigen combinations generally led to better virological outcomes in this simian immunodeficiency virus (SIV) challenge model.
Area of Science:
- Vaccinology
- Immunology
- Primate Models
Background:
- Adenovirus serotype 5 (Ad5) vectors are utilized in vaccine development.
- Simian immunodeficiency virus (SIV) is a relevant model for human immunodeficiency virus (HIV) research.
- Assessing prophylactic vaccine efficacy requires robust challenge models.
Purpose of the Study:
- To evaluate the prophylactic efficacy of multivalent replication-incompetent Ad5 vaccines against SIVmac239.
- To determine the impact of antigen breadth on vaccine effectiveness.
- To compare the efficacy of different Ad5 vaccine constructs.
Main Methods:
- Rhesus macaques were immunized with Ad5 vectors expressing SIV Gag, Pol, Nef, and Env gp140 antigens.
- Vaccine efficacy was assessed using an intrarectal high-dose SIVmac239 challenge.
- Mamu-A*01(+) and Mamu-A*01(+)/B*17(-) Indian rhesus macaques were used.
- Control groups received Ad5 vector alone.
Main Results:
- No immunological interference was observed between co-administered antigens.
- Broader antigen combinations (e.g., Gag/Pol/Nef/Env, Gag/Pol) demonstrated more favorable virological outcomes compared to narrower ones (e.g., Nef).
- Efficacy trended: Gag/Pol/Nef/Env ≈ Gag/Pol > Gag ≈ Gag/Pol/Nef > Nef, though cohort size limited precise ranking.
Conclusions:
- Multivalent Ad5-based vaccines can elicit prophylactic responses against SIV.
- Expanding the antigen coverage of Ad5 vaccines may enhance virological control.
- Further studies are warranted to confirm vaccine ranking and implications for HIV-1 vaccine development.
