Browsing Atlanta Research Conference 2021 by Author "D'Souza, Martin"
A Prophylactic Gonorrhea Vaccine: Evaluation of In vivo Immune ResponseBagwe, Priyal; Bajaj, Lotika; Gala, Rikhav; Zughaier, Susu; D'Souza, Martin (2021)Neisseria gonorrhoeae is the bacteria causing gonorrhea and has gradually developed antimicrobial resistance. Currently, there is no vaccine for gonorrhea. This study aims to investigate the immunogenicity of novel whole-cell inactivated gonococcal microparticulate vaccine formulation loaded in dissolving microneedles for skin delivery. The efficacy of vaccine formulation was assessed in vivo using female mice. The mice were immunized with a prime dose at week 0 followed by two boosters at weeks 2 and 4. Enzyme linked immunosorbent assay (ELISA) was used to measure immunoglobulin levels in collected mice sera. Formalin-fixed gonococci were intact as observed by SEM. The average length of microneedles as observed by SEM was 350 �m. ELISA demonstrated significantly higher serum immunoglobulin levels in groups receiving adjuvanted gonorrhea particulate vaccine when compared to untreated group (p<0.001). The particulate vaccine allows better uptake of antigen facilitated by the APCs causing improved antigen presentation and subsequent immune response by activation of T cells. Skin delivery of the inactivated whole-cell gonococcal microparticulate vaccine formulation loaded in dissolving microneedles is therefore an effective strategy.
Administration of a microparticulate Zika vaccine using dissolving microneedle patchesKale, Akanksha; D'Souza, Martin (2021)Zika is an infectious disease transmitted to humans through mosquito bites. It can lead to Guillain-Barré Syndrome. If transferred from mother to fetus, Zika can cause microcephaly. However, there is no approved treatment or vaccine available for Zika. Hence, we aim to develop a microparticulate vaccine for Zika and to investigate transdermal route for administration using microneedle patches to provide pain-free and needle-free immunization. PLGA microparticles (MP) encapsulating antigen (Zika PRVABC59) and adjuvants were formulated using double emulsion solvent evaporation. The size and zeta potential of MP were 573.4±10.18nm and -22.6±0.503mV. The encapsulation efficiency was 55-70%. Scanning electron microscopy showed that the MP were spherical. SDS-PAGE confirmed that the process did not affect antigen integrity. In vitro release study showed sustained release of antigen. MP were immunogenic and non-cytotoxic in vitro in dendritic cells. Subsequently, the vaccine MP with or without adjuvant MP were either injected IM or using microneedle patches via transdermal route to mice. Mice immunized with particulate vaccine produced significantly higher IgG, IgG1 and IgG2a antibody titers than the control group a robust humoral response as well as a balanced Th1/Th2 response. Antibody titers after transdermal immunization were comparable with titers after intramuscular immunization. Thus, this study established the feasibility of transdermal microneedle-based vaccine for Zika.