Publications by authors named "Aakash Mahant Mahant"
Herpes simplex virus (HSV) vaccine development has been impeded by the absence of predictive preclinical models and defined correlates of immune protection. Prior candidates elicited neutralizing responses greater than natural infection but no antibody-dependent cellular cytotoxicity (ADCC) and failed to protect in clinical trials. Primary HSV infection also elicits only neutralizing responses, but ADCC and an expanded antigenic repertoire emerge over time.
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- Antibody-dependent cellular cytotoxicity (ADCC) is important for protecting newborns from herpes, and its transfer from mother to fetus can be affected by various factors like gestational age and maternal health.
- The study showed that the transfer of HSV-neutralizing IgG was lower in preterm births compared to term births, and ADCC-mediating IgG was not effectively transferred in both term and preterm cases pre-COVID.
- Interestingly, in term dyads during the SARS-CoV-2 pandemic, there was a significant increase in the transfer of ADCC-mediating IgG, possibly due to changes in placental interactions and maternal immune responses.
Herpes simplex viruses (HSV) cause chronic infections with significant morbidity. Prior vaccines, designed to generate neutralizing antibodies (nAbs) targeting glycoprotein D (gD), failed to provide durable protection. We adopted a different strategy and evaluated a single-cycle virus deleted in gD (ΔgD-2).
View Article and Find Full Text PDFThere is an unmet need for monoclonal antibodies (mAbs) for prevention or as adjunctive treatment of herpes simplex virus (HSV) disease. Most vaccine and mAb efforts focus on neutralizing antibodies, but for HSV this strategy has proven ineffective. Preclinical studies with a candidate HSV vaccine strain, ΔgD-2, demonstrated that non-neutralizing antibodies that activate Fcγ receptors (FcγRs) to mediate antibody-dependent cellular cytotoxicity (ADCC) provide active and passive protection against HSV-1 and HSV-2.
View Article and Find Full Text PDFBackground: The glycoprotein D (gD)/AS04 vaccine failed to prevent herpes simplex virus (HSV) 2 in clinical trials. Failure was recapitulated in mice, in which the vaccine elicited neutralizing antibody but not antibody-dependent cell-mediated cytotoxicity (ADCC) responses. Preclinical findings suggest that ADCC is important for protection, but the clinical data are limited.
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- * A new approach involves a vaccine candidate called ∆gD-2, which generates a diverse response of non-gD antibodies that support immune activities like antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP), effectively protecting mice from HSV.
- * Studies indicate that the immune response from the ∆gD-2 vaccine enhances complement activation (via C1q binding), leading to better viral neutralization and cytolysis, suggesting that this candidate may offer