Eleven HIV infections during Phase II:
aidsvax.8m.com
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Human phase II studies showed that most participants developed neutralizing antibody responses against viruses of the same strain the vaccine was made from, or other closely related lab-adapted viruses. Both MN and IIIB are considered lab-adapted viruses because they are grown in laboratory cell lines. The vaccine-induced antibodies, however, were not able to neutralize "primary isolates" of HIV, that is, virus obtained from infected people. A total of 11 high-risk participants in the phase II rgp120 MN studies got infected with HIV despite being vaccinated — nine in the U.S. and two in Thailand. Breakthrough infections such as these are expected in these initial trials, and they must be carefully interpreted since these studies were not designed to demonstrate efficacy.
In a panel held during the 12th World AIDS Conference last summer in Geneva, Switzerland, VaxGen researcher Phillip Berman presented his company's scientific strategy for the development of their vaccine. Regarding the 11 breakthrough HIV infections on the rgp120 MN studies, they attribute four of them (three in the U.S. and one in Thailand) to an incomplete immunization schedule. Of the remaining seven, five were infections with a virus of a different subtype (Thailand), or a different strain (U.S.). Their conclusion is that, although their product seems to achieve some level of protection, it could be improved by adding another type of rgp120, one that is structurally similar to the most common HIV subtypes and strains in a particular country or region. This is exactly what the new "bivalent" products are. In this model, referred to as the "sieve" strategy, every successive efficacy trial will look at the HIV strains that caused the breakthrough infections, create a recombinant version of its gp120, and add it to the vaccine. In the end, a variety of polyvalent vaccines may be created. |
