Sm16 is an immunomodulatory protein that seems to play a key role in the suppression of the cutaneous inflammatory response duringSchistosoma mansonipenetration of the skin of definitive hosts. Therefore, Sm16 represents a potential target for protective immune responses induced by vaccination. In this work, we generated the recombinant protein rSm16 and produced polyclonal antibodies against this protein to evaluate its expression during different parasite life-cycle stages and its location on the surface of the parasite. In addition, we analyzed the immune responses elicited by immunization with rSm16 using two different vaccine formulations, as well as its ability to induce protection in Balb/c mice. In order to explore the biological function of Sm16 during the course of experimental infection, RNA interference was also employed. Our results demonstrated that Sm16 is expressed in cercaria and schistosomula and is located in the schistosomula surface. Despite humoral and cellular immune responses triggered by vaccination using rSm16 associated with either Freund’s or alum adjuvants, immunized mice presented no reduction in either parasite burden or parasite egg laying. Knockdown ofSm16gene expression in schistosomula resulted in decreased parasite sizein vitrobut had no effect on parasite survival or egg productionin vivo. Thus, our findings demonstrate that although the vaccine formulations used in this study succeeded in activating immune responses, these failed to promote parasite elimination. Finally, we have shown that Sm16 is not vital for parasite survival in the definitive host and hence may not represent a suitable target for vaccine development.

Background: Dose-sparing approaches can be effective in maintaining immunogenicity and safety while expanding vaccine coverage. We previously demonstrated that a half dose of ChAdOx1 nCoV-19 is as effective and immunogenic for primary vaccination. Methods: This non-inferiority, non-randomized controlled trial evaluated the effectiveness, humoral, and cellular immune responses of a third booster dose—comparing half-dose and full-dose regimens—in individuals aged 18–49 years, with a 1-year follow-up. Results: A total of 2801 participants were enrolled: 2352 received half doses and 449 received full doses. The incidence rate of COVID-19 was 225.0 per 1000 person-years in the half-dose group and 173.8 in the full-dose group, with no significant difference in effectiveness (β = −0.05; 95% CrI: −0.24 to 0.15). No deaths occurred, and hospitalization rates were similar. In a subsample (n = 558), anti-S IgG levels peaked 28 days post-dose and declined by day 180 after the primary series [175 (121–252) vs. 121 (71–208) GMT, p < 0.001], but remained elevated after the booster [192.1 (124–297) vs. 550 (380–797) GMT, p < 0.001]. Booster antibody levels were similar between groups [592.4 (318–1140) vs. 550 (380–797) GMT]. The half-dose group showed high titers against Omicron and robust T/B-cell responses (e.g., EMCD4, EMCD8, IFN⁺CD4⁺, CD19⁺TNF⁺). Conclusions: Fractional half dose of ChAdOx nCov-19 was effective and non-inferior to a full booster dose. Homologous regimen with 3 half doses or 3 full doses induced a similar increase in antibody titers and robust cellular response. ClinicalTrials.gov (NCT05059106).

The present study aimed to evaluate the kinetics of the phenotypic profile and integrative networks of T/B-cells in severe COVID-19 patients, categorized according to disease outcome, during the circulation of the B.1.1.28 and B.1.1.33 SARS-CoV-2 strains in Brazil. Peripheral blood obtained at distinct time points (baseline/D0; D7; D14-28) was used for ex vivo flow cytometry immunophenotyping. The data demonstrated a decrease at D0 in the frequency of CD3⁺ T-cells and CD4⁺ T-cells and an increase in B-cells with mixed activation/exhaustion profiles. Higher changes in B-cell and CD4⁺ T-cells at D7 were associated with discharge/death outcomes, respectively. Regardless of the lower T/B-cell connectivity at D0, distinct profiles from D7/D14-28 revealed that, while discharge was associated with increasing connectivity for B-cells, CD4⁺ and CD8⁺ T-cells death was related to increased connectivity involving B-cells, but with lower connections mediated by CD4⁺ T-cells. The CD4⁺CD38⁺ and CD8⁺CD69⁺ subsets accurately classified COVID-19 vs. healthy controls throughout the kinetic analysis. Binary logistic regression identified CD4⁺CD107a⁺, CD4⁺T-bet⁺, CD8⁺CD69⁺, and CD8⁺T-bet⁺ at D0 and CD4⁺CD45RO⁺CD27⁺ at D7 as subsets associated with disease outcomes. Results showed that distinct phenotypic timeline kinetics and integrative networks of T/B-cells are associated with COVID-19 outcomes that may subsidize the establishment of applicable biomarkers for clinical/therapeutic monitoring.