AIDSWEEKLY Plus; Monday, May 3, 1999
Daniel J. DeNoon, Senior Editor

Evidence from primate studies suggests that intravenous, envelope-based HIV vaccines can more easily protect against mucosal challenge than against intravenous challenge.

If these findings prove applicable to humans, effective HIV vaccines may depend more upon selection of the proper immunizing strain than upon sophisticated vaccine technologies.

"Parentally administered envelope-based vaccines, when given in a combination immunization regimen, may elicit protection against mucosal infection by a pathogenic uncloned virus," wrote University of Washington researcher Patricia Polacino and colleagues.

"Furthermore, contrary to some previous indications, protection may be achieved more easily against mucosal infections than against blood-borne infections."

Polacino et al. reported their findings in the Journal of Virology ("Protection of Macaques against Intrarectal Infection by a Combination Immunization Regimen with Recombinant Simian Immunodeficiency Virus SIVmne gp160 Vaccines," J Virol 1999 Apr;73(4):3134-46.

Polacino et al. used a prototype AIDS vaccine based on the simian immunodeficiency virus (SIV) strain mne (from M. nemestrina pig-tailed macaques). Recombinant vaccinia virus (New York City Board of Health strain v-NY) was engineered to express genes encoding the SIVmne gp160 envelope precursor protein. The researchers used the prime/boost method of vaccination: a priming dose of the recombinant vaccinia vaccine was followed by booster immunizations (at 2, 5, 20, and 22 months) with SIVmne gp160 protein produced in vitro by cells infected with the recombinant vaccinia virus.

In an earlier study, Polacino et al. found that cynomolgus macaques immunized in this way could resist intravenous challenge with cloned SIVmne homologous to the vaccine strain, but this protections was not very broad: only a few immunized animals resisted intravenous challenge with uncloned SIVmne (Polacino, P. et al. J Virol 1999 Jan;73(1):618-30.

In their present study, the researchers vaccinated four cynomolgus macaques. Four weeks after the last booster immunization, all four immunized animals and three control animals were challenged intrarectally with the homologous pathogenic virus clone E11S of SIVmne. All controls became infected, but three of the four immunized animals remained uninfected.

To examine the breadth of this protection, Polacino et al. then challenged the three protected animals intrarectally with uncloned SIVmne. They also administered the intrarectal challenge to three additional animals protected against intravenous challenge in their previous study.

"All six animals were boosted again with recombinant gp160 approximately two years after the initial E11S challenge," Polacino et al. noted. "Although none of these animals received any SIV antigen for more than two years, all of them showed significant recall responses upon receiving the booster immunization."

The animals received the mucosal challenge four weeks after this booster immunization. While six control animals became infected, five of the six immunized animals were protected.

Protection was correlated with the presence of neutralizing antibodies in the serum.

In an effort to explain why the vaccine offered broader protection against mucosal challenge than intravenous challenge, Polacino et al. sequenced virus obtained from peripheral blood mononuclear cells (PBMC) of animals early after infection with uncloned SIVmne by both routes. Unlike the intravenous challenge, in mucosal challenge infection was predominantly by E11S-type viruses homologous to the molecular clone from which the vaccine was made.

"Preferential transmission and/or amplification of E11S-like viruses, if confirmed, would at least partially account for the greater efficacy of the vaccine against the uncloned virus after intrarectal versus intravenous challenge," Polacino et al. wrote.

"Our results therefore also point to the importance of selecting the relevant and appropriate isolates of HIV-1 for the development of candidate vaccines. ... Our results provide a strong basis for further improvements and testing of recombinant vaccines in combination immunization strategies."

This work was supported in part by National Institutes of Health grants and contracts.

The corresponding author for this study is Shiu-Lok Hu, Department of Pharmaceutics and Regional Primate Research Center, Box 357331, University of Washington, Seattle, Washington 98195. Phone: (206) 221-4939. Fax: (206) 543-3204. Email: <hus@u.washington.edu>.

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