Deborah Heydenburg Fuller, Ph.D.

The Fuller lab is focused on investigating therapeutic and prophylactic vaccines for HIV and influenza, hepatitis B, Zika and other viral infections. In addition, we are investigating novel small protein antivirals computationally designed to mimic the binding of broadly neutralizing antibodies that bind highly conserved viral domains.

Vaccines and antivirals are the primary strategies used to combat viral infections in humans. HIV-1 and influenza pose significant challenges in that they are both highly variable viruses that rapidly evolve to evade host immunity and antiviral drugs. For HIV-1, infected individuals harbor a substantial array of HIV-1 variants, a situation that presents a daunting challenge for developing vaccines and therapies. Similarly, the worldwide variability in flu reservoirs makes it difficult to predict which flu strain might acquire the ability to infect the human population, and due to the narrow timeframe between detecting a human infection and the “predict and produce” method for generating the vaccine each season, current influenza vaccines will likely be inadequate for preventing the next flu pandemic. In an effort to address these issues, we are investigating new vaccine and antiviral concepts aimed at achieving broader, more universal protection against a wider range of highly variable viruses. Toward this goal, we have designed a therapeutic HIV DNA vaccine that when administered in combination with antiretroviral drugs to nonhuman primates infected with a primary isolate of SIV, induces profound control of viral replication that persists after antivirals are withdrawn. Viral control in this model correlated with strong mucosal CD8 responses localized in the gut, and this finding has more recently led us to investigate new DNA vaccine approaches that can more precisely focus CD8 against highly conserved epitopes and novel genetic adjuvants that can localize these responses to the gut, which is a primary source of residual virus. Similarly, using DNA vaccines and antivirals designed to precisely target highly conserved regions in influenza and other viral diseases we investigating the feasibility of achieving protection against a wide range of viral strains in mice, ferrets and nonhuman primates. These studies demonstrate the feasibility of these new platforms for achieving broad protection against HIV and influenza and other variable viruses.

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