P19-55 LB. Effective control of a pathogenic SIVmac239 challenge by a novel heterologous mucosal prime and intramuscular boost vaccine strategy
© Chen et al; licensee BioMed Central Ltd. 2009
Published: 22 October 2009
The failure of a recombinant adenovirus serotype 5 (rAd5) vector-based vaccine for HIV-1 in a phase 2b efficacy study in humans calls for efforts to develop novel vaccination strategies.
In this study, we developed a recombinant replication-competent modified vaccinia Tiantan (MVTT), namely rMVTTSIVgpe, as a mucosal vaccine expressing SIVmac Gag, Pol and Env. The immunogenicity and efficacy of rMVTTSIVgpe was studied in combination with an rAd5-based vaccine rAd5SIVgpe in Chinese macaques (Macaca mulatta) without the protective MHC class I allele Mamu-A*01. rMVTTSIVgpe was given through intranasal and oral inoculations whereas rAd5SIVgpe was given through intramuscular injection. Four macaques in each of the four study groups received the following prime and boost vaccinations: rMVTTSIVgpe/rAd5SIVgpe; rMVTTSIVgpe/rAd5SIVgpe, twice; rAd5SIVgpe/rAd5SIVgpe; and placebo controls, respectively.
We found that the heterologous rMVTTSIVgpe/rAd5SIVgpe regimen elicited cellular immune responses with enhanced magnitude, breadth, sustainability, and poly-functionality when compared with the homologous rAd5SIVgpe regimen. Higher levels of neutralizing antibody (Nab) responses were also induced by the rMVTTSIVgpe/rAd5SIVgpe regimen. These Nab responses, however, neutralized SIVmac1A11 but not SIVmac239. The additional round of rMVTTSIVgpe/rAd5SIVgpe vaccinations did not enhance the immune responses further. After intrarectal challenge with a pathogenic and Chinese macaque-adapted SIVmac239 (5 × 105 TCID50 per animal), one of four monkeys vaccinated with the rMVTTSIVgpe/rAd5SIVgpe regimen was fully protected whereas the rest showed an average of 1.96 log and 2.22 log reduction of peak and setpoint (6 weeks post challenge) viral loads as compared with control animals.
These data demonstrate that the rMVTTSIVgpe/rAd5SIVgpe regimen induced durable partial immune control of a pathogenic, neutralization-resistant SIVmac239 challenge. Our findings have critical implications for further optimization of vaccination strategies against HIV-1 by engaging the mucosal immune system.
This article is published under license to BioMed Central Ltd.