AIDSWEEKLY Plus; Monday, March 30, 1998
Daniel J. DeNoon, Senior Editor
The varicella zoster virus (VZV) vector is under development at the National Institute of Allergy and Infectious Diseases (NIAID) by Jeffrey Cohen and colleagues.
One major advantage of the vaccine is that VZV can replicate in both CD4(+) and CD8(+) T cells as well as in mononuclear cells: all targets for HIV. Moreover, a vaccinated person would have periodic reactivation of the vector.
"Thus, a VZV-[based] vaccine would provide ongoing boosting," Cohen said
Cohen discussed development of the vector in a presentation to the workshop "Virus Vectors for AIDS Vaccines" sponsored by the Division of AIDS, National Institute of Allergy and Infectious Diseases, held March 4, 1998, in Palm Springs, California, in association with the 1998 Palm Springs Symposium on HIV/AIDS.
The NIAID vector is similar to a VZV vector now being tested in Japan in a candidate herpes simplex virus (HSV) vaccine. However, the U.S. vaccine has an additional built-in safety factor: it remains sensitive to acyclovir, making it possible to kill the live virus if anything goes wrong.
A VZV vaccine potentially could be used to stimulate desired immune responses in people already infected with HIV. A good indication that it would be safe is that the currently approved live, attenuated VZV vaccine rarely causes breakthrough disease and does not increase the clinical decline of HIV infected children.
Animal studies using the NIAID VZV vector to carry HSV antigens show that while vaccinated animals become infected with HSV, they do not develop disease symptoms.
When the gene for the HIV gp160 envelope precursor protein is inserted into the VZV vector, it expresses both gp160 and the gp120 envelope protein.
Cohen said the advantages of using VZV as an HIV vaccine vector are that live VZV is already an approved vaccine, that it is safe in immunocompromised individuals, that it infects CD4 and CD8 T cells, and that its reactivation can provide durable immunity.
The disadvantages are that only a few doses can be administered before anti-VZV immune responses prevent new infections, that most adolescents and adults already are immune to VZV, that there is no good animal model for testing, and that VZV could establish latency in neuronal cells.
With regard to this last point, Cohen commented, "It is not clear what happens when gp160 is expressed in the central nervous system." Plans are under way to see whether a VZV prototype vaccine expressing SIV antigens is immunogenic in a primate model.
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