Abstract
BackgroundInduction of HIV-1-specific T-cell responses relevant to diverse subtypes is a major goal of HIV vaccine development. Prime-boost regimens using heterologous gene-based vaccine vectors have induced potent, polyfunctional T cell responses in preclinical studies.MethodsThe first opportunity to evaluate the immunogenicity of DNA priming followed by recombinant adenovirus serotype 5 (rAd5) boosting was as open-label rollover trials in subjects who had been enrolled in prior studies of HIV-1 specific DNA vaccines. All subjects underwent apheresis before and after rAd5 boosting to characterize in depth the T cell and antibody response induced by the heterologous DNA/rAd5 prime-boost combination.ResultsrAd5 boosting was well-tolerated with no serious adverse events. Compared to DNA or rAd5 vaccine alone, sequential DNA/rAd5 administration induced 7-fold higher magnitude Env-biased HIV-1-specific CD8+ T-cell responses and 100-fold greater antibody titers measured by ELISA. There was no significant neutralizing antibody activity against primary isolates. Vaccine-elicited CD4+ and CD8+ T-cells expressed multiple functions and were predominantly long-term (CD127+) central or effector memory T cells and that persisted in blood for >6 months. Epitopes mapped in Gag and Env demonstrated partial cross-clade recognition.ConclusionHeterologous prime-boost using vector-based gene delivery of vaccine antigens is a potent immunization strategy for inducing both antibody and T-cell responses.Trial RegistrationClinicalTrails.gov NCT00102089, NCT00108654
Highlights
Most viral vaccines provide protection at least partially through the induction of neutralizing antibodies [1,2]
Vaccine induction of potent, long-lived CD8+ T cells has become a major goal of current HIV-1 vaccine efforts [9]
This concept is supported by data showing that CD8+ T cell responses are associated temporally with reduction of viral load after acute infection [10,11], specific MHC class I alleles are associated with slower progression of HIV/AIDS [12,13], CD8+ T cells are largely responsible for controlling SIV viremia [14,15], and mutation of dominant CD8+ T cell epitopes is a major mechanism of immune escape in HIV and SIV infection [16,17]
Summary
Most viral vaccines provide protection at least partially through the induction of neutralizing antibodies [1,2]. SIV-specific T cell responses induced by such platforms do not protect monkeys against high dose SIV challenge, but do protect against high plasma viral burdens and loss of peripheral, and more importantly, gut-associated CD4+ memory T cells, leading to prolonged survival [22,23]. While this protection has most often been demonstrated in monkeys challenged with homologous virus (a SIV strain that matches the vaccine insert), an HIV vaccine will need to protect against the wide diversity of circulating clades of HIV. Prime-boost regimens using heterologous gene-based vaccine vectors have induced potent, polyfunctional T cell responses in preclinical studies
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
