Rama Amara, PhD

Dr. Amara is a Charles Howard Candler Professor in the Department of Microbiology and Immunology, Emory Vaccine Center, Yerkes National Primate Research Center of Emory University. He received his Ph.D. from the Indian Institute of Sciences, Bangalore, India and did his postdoctoral fellowship at Emory University. His research is focused on the development of vaccines for HIV, Tuberculosis and SARS-CoV-2 (COVID-19). Amara’s lab has pioneered the heterologous prime/boost protocols using DNA, modified vaccinia Ankara (MVA) and novel protein immunogens for vaccine delivery. A HIV vaccine based on these vectors was shown to be safe in healthy human volunteers and is currently being tested for immunogenicity and efficacy in humans. Newer versions of this vaccine using CD40L as an adjuvantthat elicit stronger humoral and cellular immune responses are under development and showed promise in the macaque model.In addition, Amara’s lab is developing novel mucosal vaccination strategies to induce a strong mucosal immunity. Amara’s lab is also developing novel therapies for HIV by targeting the PD-1 co-inhibitory pathway combined with therapeutic vaccination.More recently, Amara’s laboratory developed a MVA based vaccine for SARS-CoV-2 and showed that this vaccine induces neutralizing antibodies and T cells. He published more than 100 peer-reviewed manuscripts and received multiple grants from NIH.


ABSTRACT

There is a great need for the development of vaccines for preventing SARS-CoV-2 infection and mitigating the COVID-19 pandemic. Here, we developed two modified vaccinia Ankara (MVA) based vaccines which express either a membrane anchored full-length spike protein (MVA/S) stabilized in a prefusion state or the S1 region of the spike (MVA/S1) which forms trimers and is secreted. Both immunogens contained the receptor-binding domain (RBD) which is a known target of antibody-mediated neutralization. Following immunizations with MVA/S or MVA/S1, both spike protein recombinants induced strong IgG antibodies to purified full-length SARS-CoV-2spike protein. The MVA/S induced a robust antibody response to purified RBD, S1 and S2whereas MVA/S1 induced an antibody response to the S1 region outside of the RBD region. Both vaccines induced an antibody response in the lung and that was associated with induction of bronchus-associated lymphoid tissue. MVA/S but not MVA/S1 vaccinated mice generated robustneutralizing antibody responses against SARS-CoV-2 that strongly correlated with RBD antibody binding titers. Mechanistically, S1 binding to ACE-2 was strong but reduced following prolonged pre-incubation at room temperature suggesting confirmation changes in RBD with time. These results demonstrate MVA/S is a potential vaccine candidate against SARS-CoV-2 infection.