Plans for demonstrating these characteristics in the guinea pig model are planned, In the studies offered here, we compared HSV-2 vaccines formulated with either gD2 alone or a combination of gD2/gB2 and NE01 and evaluated prophylactic intranasal immunization. p 0.01), quantity of animals with viral shedding (50%, p 0.04) and reduction in disease positive vaginal swabs (56%, p 0.04), These data suggests that the treatment may be effective in treating chronic disease and minimizing disease transmission. These results warrant advancing the development of IN NE01-gD2/gB2 as both a prophylactic and restorative vaccine against HSV-2. checks for comparisons with equivalent variance. A value 0.05 was considered significant. Days of disease observed in each group were compared to placebo group using the chi-square test. 3.?Results 3.1. Prophylactic Immunization Studies 3.1.1. Vaccine Immunogenicity All vaccines tested elicited detectable serum antibodies against gD2 (Number 1A). The bivalent formulation IN NE01-gD2/gB2 induced significantly higher anti-gD2 antibodies compared to the monovalent formulation IN NE01-gD2 vaccine. The intramuscular alum-formulated gD2 vaccine elicited approximately 10-fold more anti-gD2 antibodies than IN NE01-gD2/gB2. As expected, the addition of the glycoprotein B2 (gB2) to the NE01-gD2/gB2 formulation lead to induction of gB2 antibodies after intranasal immunization. Open in a separate window Number. 1. Humoral immune response following three vaccinationsHumoral immune reactions elicited after immunization with numerous vaccine formulations but prior to MMV390048 HSV-2 challenge as identified from measurements of: (A) Serum IgG antibodies against gD2 and gB2 glycoproteins and, (B) serum neutralizing antibodies. Linking bars show statistical variations ( 0.05) in measured levels. Error bars are 95% CI. A similar trend was observed in the induction of neutralizing antibodies (Number 1B). Significantly higher neutralizing antibody titers were measured after immunization with the bivalent vaccine IN NE01-gD2/gB2 compared to IN NE01-gD2, but titers were still significantly lower than intramuscular immunization with IM alum/MPL-gD2. 3.1.2. Main Genital Disease As demonstrated in Number 2A, 11 of 12 animals in the control group developed primary disease having a cumulative acute mean lesion score of 9.38. All vaccinated organizations exhibited a significant reduction in imply lesion scores compared to the control group (p TSPAN11 0.003). Three out of 12 animals developed lesions in the IN NE01-gD2/gB2 group (acute cumulative imply lesion score of 0.21), two out of 12 animals developed lesions in the IM Alum/MPL-gD2 group (acute cumulative mean lesion score of 0.42), and 7 out of 12 animals developed lesions in the IN NE01-gD2 group (cumulative mean lesion score of 2.4). The acute cumulative mean lesion score of the bivalent vaccine IN NE01-gD2/gB2 group was also significantly lower (= 0.003) compared to the single antigen formulation IN NE01-gD2 group. A slight improvement (not statistically significant) in the acute cumulative imply lesion score was observed with IN NE01-gD2/gB2 versus intramuscular (IM alum/MPL-gD2) vaccination indicating related efficacy of the two vaccines for prophylaxis against HSV infections. Open in a separate window Number 2. Acute and recurrent herpetic lesion score.Cumulative mean lesion scores in guinea pigs immunized with numerous vaccine formulations prior to HSV-2 challenge. (A) Acute imply lesion scores (days 1-14). Figures to the right indicate quantity of animals developing any lesion. Bars to the right show significant variations in the cumulative imply lesion score between vaccinated organizations. (B) Recurrent mean lesion scores. Figures to the right are the quantity of animals developing any recurrent lesions. Bars to the right show significant variations in the cumulative imply lesion score between vaccinated organizations. All vaccinated organizations developed reduced scores compared to placebo for both acute and recurrent disease. 3.1.3. Main Vaginal Replication following HSV-2 Challenge Analysis of vaginal viral dropping post-challenge showed that animals vaccinated with either IN NE01-gD2/gB2 or IM Alum/MPL-gD2 experienced significantly less disease shed on days 2 and 4 post challenge. Virus detection in these 2 organizations was near the limit of detection on Day time 8 post challenge (Number 3). Open in a separate window Number 3. Viral titer post challenge.Vaginal viral shedding from swabs collected from guinea pigs post challenge. Vaginal swabs were obtained on days 2, 4, 6 and 8 following challenge with HSV-2 disease. 3.1.3. Recurrent Genital Disease Extended monitoring of the guinea pigs was performed to assess recurrent MMV390048 disease, day time15-63. Data in Number 2B show the bivalent intranasal IN NE01-gD2/gB2 vaccine exhibited significant improvement in reducing quantity of animals with recurrent lesions and the cumulative recurrent lesion scores compared to the monovalent vaccine IN NE01-gD2 (= 0.00004). MMV390048 Most notably, a remarkable and significant improvement in the reduction of the.
- T-cell epitopes are peptides derived from antigens and identified by the T-cell receptor (TCR) when bound to MHC molecules displayed within the cell surface of APCs
- Cloning of gene fragments encoding diagnostic antigens
- Epitopes are present on a single HLA (private epitope) or shared by multiple antigens (public epitope)
- Spleens were harvested in 1 (C) or 2 wpi (B, C) and cells were analyzed by movement cytometry in comparison to na?ve mice
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