AIDSWEEKLY Plus, 12 Aug 1996
Daniel J. DeNoon, Senior Editor

Nobody knows what kinds of immune responses protect people against HIV infection and/or HIV disease. But the following stories in this issue represent the world's best efforts to find out.

The best way to determine the correlates of HIV immune protection are clinical efficacy trials. Indeed, the U.S. Food and Drug Administration (FDA) has approved other vaccines, such as the acellular pertussis vaccine and the live oral typhoid vaccine, even though the correlates of protection against these diseases have never been identified.

"I always laugh when I hear that we can't do an efficacy trial because the correlates of protection are not known," Karen Goldenthal, director of vaccines and related product applications for the FDA's Center for Biologicals Evaluation and Research (CBER), recently said (AIDS Weekly, April 10, 1995). "Of course they are not known: they can only be determined in an efficacy trial."

The current debate over the testing of candidate HIV vaccines focuses not on whether to conduct efficacy trials, but on their focus and on how large they should be.

"Ten [vaccine recipients] carefully analyzed may teach us more than 100 studied perfunctorily," said John Moore of New York's Aaron Diamond AIDS Research Center at the recent XI International Conference on AIDS.

"For the next few years, the emphasis should be on analysis of the consequences of immunization, including breakthrough infections, and not on definitive endpoints of efficacy."

To facilitate analysis of trial data, an interpretive context is essential. To provide this context, researchers around the world looked in four places for insights into the correlates of immunity to HIV:

• People who remain uninfected despite repeated exposure to HIV,
• People who remain healthy despite long-term HIV infection,
• Non-human primates protected against challenge retrovirus infection by prototype HIV and SIV vaccines, and
• Human recipients of experimental HIV vaccines. Some of the data from previous studies has shown that:
• Vigorous HIV specific cytotoxic lymphocyte (CTL) responses and paradoxically weak neutralizing antibody activity characterize the immune responses of long-term survivors with the lowest viral loads (AIDS Res H, 1996;12(7):585-592, see AIDS Weekly Plus, June 3, 1996).
• A third of HIV negative intravenous drug users (IVDUs) tested by an Italian/American research team had antibodies that recognized both HIV and human self antigens. Moreover, more than three-fourths of these high-risk individuals had helper T cells that produced interleukin 2 (IL-2) in response to HIV envelope peptides (J Inf Dis, 1996:173(2):472-476, see AIDS Weekly Plus, April 29, 1996).
• Study findings suggest that a vaccine capable of stimulating mucosal immunity could protect against HIV infection. Some U.S. women in high-risk exposure groups remain HIV seronegative and uninfected but have local mucosal antibodies that recognize the HIV gp120 antigen.(AIDS Weekly, January 15, 1996).

The articles that follow are reports of presentations made during a session of the 1996 XI International Conference on AIDS entitled "Vaccines: Are Correlates of Protection?"

The various studies approach the question from different directions, and sometimes yield conflicting data. But when the time comes to assess the results of HIV vaccine efficacy trials or to design improved vaccines, these groundbreaking studies will prove invaluable.

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