AIDSWEEKLY Plus; Monday, May 11, 1998
Daniel J. DeNoon, Senior Editor
The recombinant NYVAC-SIV vaccine encodes simian immunodeficiency virus (SIV) antigens in an attenuated vaccinia virus. A human version of the vaccine (using the ALVAC canarypox vector is under development by Virogenetics Inc. in cooperation with Pasteur-Merieux-Conaught; human trials are already underway.
Vaccinated animals were challenged with the notoriously pathogenic SIVmac251. Only a live, attenuated SIV vaccine has been able to protect animals against intravenous challenge with this virus.
Five of 11 vaccinated animals resisted infection after intrarectal challenge with SIVmac251. All 12 vaccinated animals challenged intravenously with SIVmac251 became infected, but four apparently controlled viral expression and had slow disease progression. All control animals but one became infected and died of AIDS-like disease; the sole surviving animal has drastically declining CD4 counts typical of AIDS.
"The fact that the NYVAC-SIV recombinant vaccine appears to be effective per se in the animal model that best mirrors human AIDS supports the idea that the development of a highly attenuated poxvirus-based vaccine candidate can be a valuable approach to significantly decrease the spread of human immunodeficiency virus (HIV) infection by the human route," wrote J. Benson of the National Cancer Institute, Bethesda, Maryland, and colleagues.
Benson et al. reported their findings in the Journal of Virology ("Recombinant Vaccine-Induced Protection against the Highly Pathogenic Simian Immunodeficiency Virus SIVmac251: Dependence on Route of Challenge Exposure," J Virol, 1998;72(5):4170-82).
The authors noted that use of HIV blood tests in much of the world has reduced HIV transmission by intravenously administered blood.
"Thus vaccine approaches that decrease mucosal transmission without necessarily protecting against intravenous infection could have an impact on the HIV epidemic," they wrote.
NYVAC is a highly attenuated strain of vaccinia virus derived from a plaque-cloned isolate of the Copenhagen vaccine strain by the deletion of 18 open reading frames (ORFs) from the viral genome. Animal studies showed NYVAC to be without many of the deleterious effects seen in infection with whole vaccinia virus - including the dissemination of the virus in immunosuppressed mice. Despite this high degree of attenuation, evidence suggests that the virus is capable of inducing immune responses to foreign antigens.
The NYVAC-SIV vaccine expresses the SIV gag, pol, and env genes in the highly attenuated NYVAC vaccinia vector. Because cell-mediated immunity is thought to be important for protection against HIV and SIV, a second vaccine was created expressing the (alpha) and (beta) chains of human interleukin 12 (IL-12) and IL-2, cytokines known to increase cell-mediated immune responses and suppress humoral immune responses.
Half of the vaccinated animals received both vaccines simultaneously and half received only NYVAC-SIV. Although the IL-12 vaccine acted as had been hoped - greatly increasing cell-mediated responses at the expense of humoral responses - it offered no additional benefit.
"The outcome of this study indicates that vaccination with NYVAC-SIV alone was able to protect macaques from an SIVmac251 mucosal challenge exposure and appears to slow disease progression following intravenous SIVmac251 inoculation," Benson et al. wrote. "Further, the results illustrate the ability to modulate measurable immune responses by cytokine administration without an effect on vaccine efficacy."
The researchers argued that even though most animals became infected, the study demonstrated the promise of the NYVAC approach.
"We believe that the induction of long-lasting protective immunity in five of 11 animals following mucosal challenge and the apparent prevention of disease progression in a portion of infected vaccinees following intravenous exposure in this perhaps-too-vigorous animal model validate the usefulness of this vaccine approach and warrant further research on how to reach protection in a higher portion of the vaccinated animals," they concluded. "Evaluation of NYVAC recombinant vaccines in combination with other vaccine approaches may help in this endeavor."
This study was supported in part by Pasteur-Merieux- Conaught.
The corresponding author for this study is G. Franchini, Basic Research Laboratory, National Cancer Institute, 37 convent Dr., Bldg. 37, Rm. 6A11, Bethesda, Maryland. Phone: (301) 496-6007. Fax: (301) 496-8394. Email: <veffa@helix.nih.gov>.
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