The Changing Face of HIV Vaccine Research
A summary of and comments on Gary Nabel, M.D., Ph.D. ( Director of the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases in Maryland) oral presentation during the first plenary session of the 2011 Rome IAS conference: July 18th, 2011.
Gary Nabel, Director of the Vaccine Research Center at the NIAID in the United States gave the first plenary lecture of the meeting on Monday 18.
He first noted that despite the exceptional challenge posed by an AIDS vaccine research, optimism is still possible due to recent advances in the field. Four efficacy trials have been now completed. The first one used, in the late 90s, gp120 and was a failure. But there was recently the modest efficacy of the RV144 trial conducted in Thailand, that can be considered as a proof of concept that a vaccine can prevent HIV transmission. Its efficacy was only 31% and limited in time. HVTN 505 is an ongoing trial addressing both the induction of humoral and cellular immunity. Enrolment will end in 2012.
Making a vaccine has been difficult first because of the genetic diversity of HIV. Then, the virus constantly changes when an immune response against it appears. The HIV envelop is divided into 3 parts. The CD4 binding site cannot mutate. It is therefore a site whe have to focus on. But glycans mask Env and it cannot be recognized by the immune system. So we had to make in the laboratory forms of this molecule, and create a probe able to bind with antibodies. This probe was then used to identify antibodies in patients. And, it is now clear that a substantial proportion of HIV-infected individuals (10-25%) develop broadly neutralizing antibodies. Several antibodies have been isolated, like the VRC01 which neutralizes more than 90% of naturally circulating viruses. It recognizes the highly conserved CD4bs (CD4 binding site) of the viral envelop required for entry. In animal models, generating these antibodies protected against rectal or vaginal challenge.
Work is ongoing to see if passive transfer of these antibodies can protect animals. There are thousands of similar neutralizing antibodies in patients, coming all from the same gene, but the B cell precursor of VRC01 does not recognize Env as proved by deep sequencing. Novel immunogen trimers are now developed that can elicit CD4bs antibodies in animals, but the degree of neutralization is still insufficient.
However, despite these advances, it remains a challenge to develop a vaccine because there is only a very small window for the antibody to get to its site. Much work remains to be done and devotion to making a vaccine has to be continued, Gary Nabel concluded.
Key words: HIV, HIV prevention, HIV vaccine