Avan Antia
Program: Molecular Microbiology and Microbial Pathogenesis
Current advisor: Siyuan Ding, PhD
Undergraduate university: University of Maryland-College Park
Research summary
Although the majority of microbial pathogens enter through the host mucosa, there are few licensed mucosal vaccines available. Unlike injectable vaccines, mucosal vaccines induce local IgA and can thus prevent initial infection and subsequent transmission. Microfold (M) cells, located on Peyer’s patches within the small intestine, facilitate the sampling of luminal antigens and subsequent intestinal IgA production. While M cells are essential for mucosal IgA response to commensal bacteria and certain protein antigens, their immunological role in enteric virus infections has not been investigated. Antigen-specific intestinal IgA correlates with protection against clinically relevant enteric viruses, such as rotavirus. Here, we utilize rotavirus to investigate the role of M cells in natural enteric viral infection and vaccine-induced humoral immunity. We employ a conditional M cell knockout mouse model (Villin-Cre+ RANKfl/fl, or RANK∆IEC) that lacks RANK expression in intestinal epithelial cells (IEC) and floxed control mice (Cre-RANKfl/fl) to investigate both mucosal and systemic immune response to rotavirus. We find that unlike in the case of protein antigens and commensal bacteria, M cells are not broadly required for immune response to enteric virus, but rather they are required in a context-dependent basis. Specifically, we find that oral murine rotavirus infection induces comparable levels of anti-rotavirus intestinal IgA in control RANKfl/fl mice and M cell-deficient RANK∆IEC mice. In contrast, low dose live-attenuated rhesus rotavirus elicits suboptimal anti-rotavirus IgA responses in RANK∆IEC mice, which remain partially susceptible to reinfection by murine rotavirus. Oral inoculation with inactivated rotavirus or replication-deficient adenoviral-vectored rotavirus vaccine does not induce detectable intestinal antigen-specific IgA production in RANK∆IEC mice, which, unlike RANKfl/fl mice, are fully susceptible to viral challenge. Finally, we find that following oral infection and immunization, intestinal M cells are required for the production of antigen specific serum IgA, but not serum IgG, and consequently RANK∆IEC mice have fewer numbers of rotavirus-specific IgA+ antibody secreting cells in the mesenteric lymph node and bone marrow. Collectively, our studies advance our understanding of the protective, yet context dependent, role of M cells against enteric virus infection and pave the way for developing improved oral vaccines.
Graduate publications
Antia A, Alvarado DM, Ding S, Ciorba MA. 2022 Adding Fuel to The Fire? A Role of Intraepithelial Lymphocytes in Enteric Immune Responses to SARS-CoV-2 Infection. Gastroenterology, ():S0016-5085(21)04120-2.
Antia A, Pinski AN, Ding S. 2022 Re-Examining Rotavirus Innate Immune Evasion: Potential Applications of the Reverse Genetics System. mBio, ():e0130822.
Antia A, Alvarado DM, Zeng Q, Casorla-Perez LA, Davis DL, Sonnek NM, Ciorba MA, Ding S. 2022 SARS-CoV-2 Omicron (BA.1) variant infection of human colon epithelial cells. Viruses, 16(4):634.