Browsing by Author "Berendam, Stella J"

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    Conjugation of HIV-1 envelope to hepatitis B surface antigen alters vaccine responses in rhesus macaques.
    (NPJ vaccines, 2023-11) Nettere, Danielle; Unnithan, Shakthi; Rodgers, Nicole; Nohara, Junsuke; Cray, Paul; Berry, Madison; Jones, Caroline; Armand, Lawrence; Li, Shuk Hang; Berendam, Stella J; Fouda, Genevieve G; Cain, Derek W; Spence, Taylor N; Granek, Joshua A; Davenport, Clemontina A; Edwards, Robert J; Wiehe, Kevin; Van Rompay, Koen KA; Moody, M Anthony; Permar, Sallie R; Pollara, Justin
    An effective HIV-1 vaccine remains a critical unmet need for ending the AIDS epidemic. Vaccine trials conducted to date have suggested the need to increase the durability and functionality of vaccine-elicited antibodies to improve efficacy. We hypothesized that a conjugate vaccine based on the learned response to immunization with hepatitis B virus could be utilized to expand T cell help and improve antibody production against HIV-1. To test this, we developed an innovative conjugate vaccine regimen that used a modified vaccinia virus Ankara (MVA) co-expressing HIV-1 envelope (Env) and the hepatitis B virus surface antigen (HBsAg) as a prime, followed by two Env-HBsAg conjugate protein boosts. We compared the immunogenicity of this conjugate regimen to matched HIV-1 Env-only vaccines in two groups of 5 juvenile rhesus macaques previously immunized with hepatitis B vaccines in infancy. We found expansion of both HIV-1 and HBsAg-specific circulating T follicular helper cells and elevated serum levels of CXCL13, a marker for germinal center activity, after boosting with HBsAg-Env conjugate antigens in comparison to Env alone. The conjugate vaccine elicited higher levels of antibodies binding to select HIV Env antigens, but we did not observe significant improvement in antibody functionality, durability, maturation, or B cell clonal expansion. These data suggests that conjugate vaccination can engage both HIV-1 Env and HBsAg specific T cell help and modify antibody responses at early time points, but more research is needed to understand how to leverage this strategy to improve the durability and efficacy of next-generation HIV vaccines.
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    Maternal Fc-mediated non-neutralizing antibody responses correlate with protection against congenital human cytomegalovirus infection.
    (The Journal of clinical investigation, 2022-08) Semmes, Eleanor C; Miller, Itzayana G; Wimberly, Courtney E; Phan, Caroline T; Jenks, Jennifer A; Harnois, Melissa J; Berendam, Stella J; Webster, Helen; Hurst, Jillian H; Kurtzberg, Joanne; Fouda, Genevieve G; Walsh, Kyle M; Permar, Sallie R
    Human cytomegalovirus (HCMV) is the most common congenital infection and a leading cause of stillbirth, neurodevelopmental impairment, and pediatric hearing loss worldwide. Development of a maternal vaccine or therapeutic to prevent congenital HCMV has been hindered by limited knowledge of the immune responses that protect against HCMV transmission in utero. To identify protective antibody responses, we measured HCMV-specific IgG binding and antiviral functions in paired maternal and cord blood sera from HCMV-seropositive transmitting (n = 41) and non-transmitting (n = 40) mother-infant dyads identified via a large, US-based, public cord blood bank. We found that high-avidity IgG binding to HCMV and antibody-dependent cellular phagocytosis (ADCP) were associated with reduced risk of congenital HCMV infection. We also determined that HCMV-specific IgG activation of FcγRI and FcγRII was enhanced in non-transmitting dyads and that increased ADCP responses were mediated through both FcγRI and FcγRIIA expressed on human monocytes. These findings suggest that engagement of FcγRI/FcγRIIA and Fc effector functions including ADCP may protect against congenital HCMV infection. Taken together, these data can guide future prospective studies on immune correlates against congenital HCMV transmission and inform HCMV vaccine and immunotherapeutic development.