Important note: Information in this article was accurate in March 1999. The state of the art may have changed since the publication date.AIDSWEEKLY Plus; Monday, March 15, 1999
Daniel J. DeNoon, Senior Editor
Researchers at the U.S. National Institute of Allergy and Infectious Diseases (NIAID) think it can.
Live, attenuated vaccinia is the basis of the hugely successful smallpox vaccine - and, indeed, gave the world the word "vaccine." Several research teams have constructed versions of recombinant vaccinia capable of expressing HIV antigens. But the NIAID team is perhaps the most persistent.
"We believe that this is a very promising viral vector for pursuit of an AIDS vaccine," said NIAID's Vanessa M. Hirsch in a symposium presentation to the 6th Conference on Retroviruses and Opportunistic Infections, held January 31-February 4, 1999, in Chicago, Illinois.
Hirsch and colleagues are using the modified vaccinia Ankara (MVA) to carry HIV antigens. MVA actually has been used as a smallpox vaccine and thus has an established safety record based on some 120,000 human immunizations. It uses the thymidine kinase (TK) enzyme and thus can be selectively treated with available TK inhibitors in case it gets out of hand. However, all of the MVA immune-evasion genes have been deleted, and it has a severely restricted host range. As a vaccine vector it is under investigation for use in vaccines against influenza, tumors, and malaria.
"The question isn't about safety, it's about how they work as vaccines," Hirsch said.
Prototype AIDS vaccines employ simian immunodeficiency virus (SIV) antigens. New MVA constructs carry the SIV envelope (env), gag, and pol genes in various combinations under the control of a strong promoter sequence. Cells infected with this recombinant MVA produce virus-like particles (VLPs) that strongly resemble the wild-type virus.
The SIV vaccines were given to four groups of six macaques at months 0, 1, 4, and 7. The animals received either MVAgag-pol, MVAenv, MVAgag-pol-env, or MVA without SIV insertions.
Upon challenge with pathogenic SIV at month 8, all of the immunized animals became infected. However, the immunization with SIV antigens significantly altered the course of infection with mean challenge-virus titers lower in the treated monkeys.
"We have quite a few animals who are still doing well," Hirsch said. "Functional Gag-specific CTL are seen after the first two immunizations. Further vaccinations did not further increase this response."
Other experimental AIDS vaccines are based on avian poxviruses, most notably the Virogenetics/Pasteur-Merieux-Connaught canarypox- based ALVAC. But Hirsch said that the MLV vaccine may prove superior.
"Direct comparisons have not been made, but I think MVA is quite a bit better than ALVAC in terms of immunogenicity," she said.
The NIAID team proposes that MLV vaccines be further developed with an eye to human clinical trials.
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