[Show abstract][Hide abstract] ABSTRACT: This study analyzed a heterologous prime-boost vaccine approach against HIV-1 using three different antigenically unrelated negative-stranded viruses (NSV) expressing HIV-1 Gag as vaccine vectors: rabies virus (RABV), vesicular stomatitis virus (VSV) and Newcastle disease virus (NDV). We hypothesized that this approach would result in more robust cellular immune responses than those achieved with the use of any of the vaccines alone in a homologous prime-boost regimen. To this end, we primed BALB/c mice with each of the NSV-based vectors. Primed mice were rested for thirty-five days after which we administered a second immunization with the same or heterologous NSV-Gag viruses. The magnitude and quality of the Gag-specific CD8(+) T cells in response to these vectors post boost were measured. In addition, we performed challenge experiments using vaccinia virus expressing HIV-1 Gag (VV-Gag) thirty-three days after the boost inoculation. Our results showed that the choice of the vaccine used for priming was important for the detected Gag-specific CD8(+) T cell recall responses post boost and that NDV-Gag appeared to result in a more robust recall of CD8(+) T cell responses independent of the prime vaccine used. However, the different prime-boost strategies were not distinct for the parameters studied in the challenge experiments using VV-Gag but did indicate some benefits compared to single immunizations. Taken together, our data show that NSV vectors can individually stimulate HIV-Gag specific CD8(+) T cells that are effectively recalled by other NSV vectors in a heterologous prime-boost approach. These results provide evidence that RABV, VSV and NDV can be used in combination to develop vaccines needing prime-boost regimens to stimulate effective immune responses.
PLoS ONE 01/2013; 8(6):e67123. · 3.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Correlates of protection (CoPs) against infection by primate lentiviruses remain undefined. Modest protection against HIV-1 was observed in one human vaccine trial, whereas previous trials and vaccine-challenge experiments in non-human primates have yielded inconsistent but intriguing results. Although high levels of neutralizing antibodies are known to protect macaques from mucosal and intravenous viral challenges, antibody or other adaptive immune responses associated with protection might also be mere markers of innate immunity or susceptibility. Specific strategies for augmenting the design of both human trials and animal experiments could help to identify mechanistic correlates of protection and clarify the influences of confounding factors. Robust protection may, however, require the combined actions of immune responses and other host factors, thereby limiting what inferences can be drawn from statistical associations. Here, we discuss how to analyze immune protection against primate lentiviruses, and how host factors could influence both the elicitation and effectiveness of vaccine-induced responses.
[Show abstract][Hide abstract] ABSTRACT: Soon after HIV was discovered as the cause of AIDS in 1983-1984, there was an expectation that a preventive vaccine would be rapidly developed. In trying to achieve that goal, three successive scientific paradigms have been explored: induction of neutralizing antibodies, induction of cell mediated immunity, and exploration of combination approaches and novel concepts. Although major progress has been made in understanding the scientific basis for HIV vaccine development, efficacy trials have been critical in moving the field forward. In 2009, the field was reinvigorated with the modest results obtained from the RV144 trial conducted in Thailand. Here, we review those vaccine development efforts, with an emphasis on events that occurred during the earlier years. The goal is to provide younger generations of scientists with information and inspiration to continue the search for an HIV vaccine.
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