HIV, TB, and Malaria Vaccine Development for Africa (PO1)

In 2002, Dr. Barton Haynes received a PO1 grant from the NIH titled, “HIV, TB, and Malaria Vaccine Development for Africa.” Through this PO1, DHVI investigators are attempting to develop a trivalent vaccine for HIV, TB and malaria for children.

 

Dr. Haynes, Dr. Larry Liao, Dr. David Montefiori, Jae-Sung Yu, and James Peacock are currently working on PO1 Project 4 titled, “HIV Neutralizing Antibody Immunogens for Expression in Attenuated Mycobacteria.” A significant part of the project involves generating recombinant vaccinia viruses (rVV) that will allow investigators to express recombinant HIV-1 envelope proteins, HIV-1 gp120 and gp140. They can then induce neutralizing antibodies against the HIV-1 primary isolates derived from these proteins in order to determine which isolates produce the best immune responses in guinea pigs. The Molecular and Immunology Core (Core C) led by David Montefiori, Larry Liao, Feng Gao, and Herman Staats is collaborating on the Project in the development of optimal HIV-1 immunogens.

 

Investigators are also contributing to this vaccine development by expressing HIV-1 gp120 and gp140 in Mycobacterium smegmatis (rSmeg), BCG and attenuated MTB in order to determine their ability to induce anti-HIV T cell responses at systemic and mucosal sites.

 

Finally, DHVI investigators focused on studying the relationship between cardiolipin and HIV-1 immunity. Current vaccines derived from HIV-1 envelope proteins have not been able to successfully induce broadly reactive neutralizing antibodies in HIV-1 infected patients. HIV-1 patients can, however, produce polyclonal antibodies when their B cells react with the endogenous phospholipid called cardiolipin. Investigators hypothesized that cardiolipin could, therefore, induce an immune response to human monoclonal antibodies. In order to test their theory, they assayed two rare MAbs with broadly neutralizing activity, 2F5 and 4E10, along with 33 other anti-HIV-1 MAbs for cardiolipin and other autoantigen reactivities. They found that 2F5 and 4E10 both reacted with cardiolipin while the 33 other MAbs did not. Future plans include studying the rare number of patients with SLE and anti-phospholipid syndrome (APS) who developed HIV-1 infection to find out if they make anti-membrane proximal antibodies, which neutralize HIV.