Analysis of T cell responses to chimpanzee adenovirus vectors encoding HIV gag–pol–nef antigen

S Herath,A Le Heron,S Colloca,P Bergin,S Patterson,J Weber,R Tatoud,G Dickson

doi:10.1016/j.vaccine.2015.10.111

S Herath, A Le Heron + Show 6 more

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Adenoviruses have been shown to be both immunogenic and efficient at presenting HIV proteins but recent trials have suggested that they may play a role in increasing the risk of HIV acquisition. This risk may be associated with the presence of pre-existing immunity to the viral vectors. Chimpanzee adenoviruses (chAd) have low seroprevalence in human populations and so reduce this risk. ChAd3 and chAd63 were used to deliver an HIV gag, pol and nef transgene. ELISpot analysis of T cell responses in mice showed that both chAd vectors were able to induce an immune response to Gag and Pol peptides but that only the chAd3 vector induced responses to Nef peptides. Although the route of injection did not influence the magnitude of immune responses to either chAd vector, the dose of vector did. Taken together these results demonstrate that chimpanzee adenoviruses are suitable vector candidates for the delivery of HIV proteins and could be used for an HIV vaccine and furthermore the chAd3 vector produces a broader response to the HIV transgene.

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The search for an effective, prophylactic HIV vaccine has been complicated by evidence that pre-existing immunity to some of the most commonly used human recombinant adenovirus-based viral vectors have suppressed the effectiveness of vaccination and may have enhanced the risk of HIV infection in some clinical trial populations [1,2,3]
Cells infected with ChAd type 3 (chAd3)-GPN and chAd type 63 (chAd63)-GPN produced 48.2% and 79.3% Gag positive cells, respectively (Fig. 1B, right hand plots) whereas cells infected with negative control, subtype-matched env bearing viruses were negative for anti-gag antibody staining
When injected at an equal infectious unit dose, both vectors induced a response to each of the transgene products, except for Nef, and chAd3 stimulated a higher IFN␥ response compared to chAd63 (Fig. 2)

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Introduction

The search for an effective, prophylactic HIV vaccine has been complicated by evidence that pre-existing immunity to some of the most commonly used human recombinant adenovirus (rAd)-based viral vectors have suppressed the effectiveness of vaccination and may have enhanced the risk of HIV infection in some clinical trial populations [1,2,3]. Alternative human rAd HIV vaccines, based on strains less prevalent in humans have been shown to be immunogenic (reviewed in [5]). ChAd type 3 (chAd3) and chAd type 63 (chAd63) have low seroprevalence within the populations from Africa, the Americas and India and when encoding HIV or SIV gag as a transgene were as effective as Ad5 at eliciting a T cell responses and compared favourably to alternative human rAds [9]. ChAd3 encoding Gag/Pol from SIV strain mac239 induced comparable CD8 T cell immunity to rAd5 in mice and a chAd63 vectored vaccine with an antigen based on conserved HIV-1 subprotein regions has been tested and shown to be safe and immunogenic in humans [10,11]. ChAd3 and 63 vectors have been tested, with promising results, as vaccines for Hepatitis C, Malaria, Respiratory Syncytial Virus and Ebola [12,13,14,15]

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