Santra, S. et al. Heterologous prime/boost immunizations of rhesus monkeys using chimpanzee adenovirus vectors. Vaccine 27, 5837-5845

Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Vaccine (Impact Factor: 3.62). 09/2009; 27(42):5837-45. DOI: 10.1016/j.vaccine.2009.07.050
Source: PubMed


Pre-existing immunity to human adenovirus serotype 5 (AdHu5) has been shown to suppress the immunogenicity of recombinant Ad5 (rAdHu5) vector-based vaccines for human immunodeficiency virus type 1 (HIV-1) in both preclinical studies and clinical trials. As a potential solution to this problem we developed adenovirus vaccine vectors of chimpanzee origin. In the present study we assessed the immunogenicity of various chimpanzee adenovirus vectors in a prime/boost regimen to HIV-1 envelope and SIV Gag-Pol in rhesus monkeys and their ability to protect against pathogenic viral challenge. Although rAdHu5-primed monkeys had higher magnitude T cell responses than rAdC7 or rAdC68 prior to challenge, the rAdC7-rAdC1/C5 and rAdHu5-rAdC1/C5 immunizations resulted in comparable magnitude recall cellular immune responses and comparable level of control of viremia post-challenge.

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    • "Blood was collected by submandibular bleeding and placed into 4% sodium citrate. Peripheral blood mononuclear cells were harvested as described (Santra et al., 2009). "
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    • "Ad-C68 was shown to be effective at inducing anti-rabies neutralizing antibodies and may be capable of inducing anti-HIV-1 gag CTL immune responses [21, 156]. Santra et al. confirmed that simian Ads C7, C68 and chimeric C1/C5 were capable of inducing immune responses in the presence of pre-existing immunity and could be used in prime/boost immunization strategies [157]. In addition to their use as vaccine vectors a simian adenovirus ChAd3 was shown to be effective at expressing carcinoembryonic antigen (CEA) and was as robust as huAd5 at breaking tolerance and successfully overcoming tumorigenicity in the presence of huAd5 pre-existing immunity [158]. "
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