Prof Nancy Haigwood
Dr. Haigwood's laboratory has a long-standing interest in the HIV Envelope glycoprotein (Env) that has led to a current focus in three overlapping areas of research: 1) neutralizing antibodies (NAbs) directed to the HIV and SIV Env; 2) mother-to-child transmission (MTCT) of HIV/SIV; and 3) HIV vaccine development. Env glycoproteins play a major role in immunity and host defense in the primate lentiviruses. Her group has investigated the role of SIV and HIV Envelope-specific NAbs in immune control and as potential therapeutic entities in nonhuman primate (NHP) models. In 1991, they were the first toshow that NAbs in human subjects with broad activity are directed to conformational determinants. They have used nonhuman primate (NHP) models to test concepts, reviewed in 2015. In the SIV system in 1996 and in 2004, the group found that time to disease was significantly lengthened by passive treatment with NAbs (IgG) during acute infection. Importantly, the presence of NAbs during acute SIV infection accelerated the development of effective NAbs, a novel finding that has implications for both vaccines and for therapies. The Haigwood group is currently studying HIV-1 in humans and SIV and SHIV in NHPs to explore the development of NAbs in relationship to changing Env variants. They showed that NAbs are dynamic, even in those HIV-positive individuals with a high degree of control for many years, so-called "controllers." A second major goal of Dr. Haigwood's group is to understand the role of NAbs in MTCT. Using the virus SHIV-SF162P3, the group has studied transmission from pregnant macaques to their infants, and oral infection of newborns, where this virus is highly pathogenic. These studies (2007, 2010, 2013, and 2016) showed that NAbs have a novel role in controlling viremia and enhancing B cell responses in vivo, resulting in significant protection from disease. These data provide evidence for additional beneficial roles for NAbs beyond direct protection. Using human monoclonal antibodies given as passive therapies to limit MTCT, and they have shown that these antibodies can clear early foci of infection and prevent establishment of the viral reservoir. This establishes a new paradigm for antibodies in the antiviral approaches.
Sponsored by Australian Society of Immunology