Interchangeability of different COVID-19 vaccine platforms as booster doses: A phase 3 study mimicking real-world practice.

BACKGROUND: The COVID-19 pandemic is over but the highly immunized or naturally exposed global population still requires booster vaccinations against newly emerging SARS-CoV-2 variants. We assessed safety and immunogenicity of booster doses of COVID-19 vaccines based on three different platforms in a setting that mimics the current routine practice in Brazil. METHODS: In this phase 3 study from 14 February 2023 to 12 June 2023 we enrolled previously immunized adults to receive an additional booster dose of one of three vaccines. Immunogenicity against ancestor SARS-CoV-2 and Omicron BF.7, BQ.1.1.3, and XBB.1.5.6 sub-lineages was measured as ELISA IgG or virus neutralizing (VNT) antibodies and safety/reactogenicity assessed using diary cards. RESULTS: Volunteers with a history of full primary COVID-19 immunization striated to three cohorts according to their previous booster vaccination history-0 (n = 26), 1 (n = 140) or 2 (n = 606) booster vaccinations-were randomized 2:1:1 to receive either recombinant protein (SCB-2019, Clover), adenovirus-vector (ChAdOx1-S, AstraZeneca/Fiocruz), or mRNA (BNT162b2, Pfizer/Wyeth). Baseline antibody titers were higher in individuals who had received one or two boosters and titers against both ancestor and Omicron sub-lineages increased in all groups regardless of the number of previous booster doses or the vaccine used. Day 28 geometric mean titers (GMTs) and geometric mean-fold rises (GMFR) against all variants were higher after BNT162b than SCB-2019 or ChAdOx1-S, but BNT162b groups displayed more rapid antibody waning at Day 84. Within cohorts each vaccine elicited similar GMFR against the different SARS-CoV-2 strains. All vaccines were well tolerated with similar solicited reactogenicity profiles. CONCLUSIONS: Protein, adenovirus-vector or mRNA vaccine boosters were equally well tolerated and immunogenic against ancestor SARS-CoV-2 and Omicron sub-lineages in fully primed adults with 0-2 prior boosters. BNT162b induced the highest immune responses but also the most rapid waning of antibodies 3 months after vaccination. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT05812586.

COVID-19 site readiness initiative: Building clinical trial capacity for vaccine efficacy trials in Latin America in response to the pandemic.

According to the World Health Organization, the American region has the highest coronavirus disease-2019 (COVID-19) cases and deaths since the start of the pandemic. This humanitarian tragedy presented the possibility of generating efficacy data from COVID-19 vaccine trials. The race to develop successful vaccines imposed a high demand for trained healthcare personnel and clinical sites where large scale randomized clinical trials could be conducted. This site readiness initiative, funded by the Bill and Melinda GatesFoundation (BMGF), was carried out to rapidly build site capacity for running COVID-19 vaccine trials in Latin America. Twenty-two sites across 7 countries were selected and received funding. Site selection was based on defined feasibility criteria which deemed these sites as suitable for running vaccine efficacy trials. Criteria for selection included investigator and core permanent staff experience, public health measures in place for COVID-19, import/export requirements for study drug and biological specimens, a clear and accelerated ethical and regulatory approval process for COVID-19 trials. Training was tailored and delivered according to the experience level of the investigator and site staff, and included GCP training, standard operating procedures (SOP) fundamentals, conducting vaccine trials, COVID-19 pathophysiology, and vaccine trials lessons learned. Most of the grant funds were utilized for space expansion and renovation (46 %) followed by purchase of equipment (36 %); the remaining 18 % was spent on human resources. By the end of this site readiness initiative project, which took approximately 4 months, 21 of 22 (95 %) sites had agreements in place or were in discussions with sponsors to conduct large scale COVID-19 vaccine trials.

Association of Anti-Rotavirus IgA Seroconversion with Growth, Environmental Enteric Dysfunction and Enteropathogens in Rural Pakistani Infants.

BACKGROUND: The underperformance of oral vaccines in children of low- and middle-income countries is partly attributable to underlying environmental enteric dysfunction (EED). METHODOLOGY: We conducted a longitudinal, community-based study to evaluate the association of oral rotavirus vaccine (Rotarix®) seroconversion with growth anthropometrics, EED biomarkers and intestinal enteropathogens in Pakistani infants. Children were enrolled between three to six months of their age based on their nutritional status. We measured serum anti-rotavirus immunoglobulin A (IgA) at enrollment and nine months of age with EED biomarkers and intestinal enteropathogens. RESULTS: A total of 391 infants received two doses of rotavirus (RV) vaccine. 331/391 provided paired blood samples. Of these 331 children, 45% seroconverted at 9 months of age, 35% did not seroconvert and 20% were seropositive at baseline. Non-seroconverted children were more likely to be stunted, wasted and underweight at enrollment. In univariate analysis, insulin-like growth factor (IGF) concentration at 6 months were higher in seroconverters, median (25th, 75th percentile): 26.3 (16.5, 43.5) ng/ml vs. 22.5 (13.6, 36.3) ng/ml for non-seroconverters, p-value = 0.024. At nine months, fecal myeloperoxidase (MPO) concentrations were significantly lower in seroconverters, 3050(1250, 7587) ng/ml vs. 4623.3 (2189, 11650) ng/ml in non-seroconverted children, p-value = 0.017. In multivariable logistic regression analysis, alpha-1 acid glycoprotein (AGP) and IGF-1 concentrations were positively associated with seroconversion at six months. The presence of sapovirus and rotavirus in fecal samples at the time of rotavirus administration, was associated with non-seroconversion and seroconversion, respectively. CONCLUSION: We detected high baseline RV seropositivity and impaired RV vaccine immunogenicity in this high-risk group of children. Healthy growth, serum IGF-1 and AGP, and fecal shedding of rotavirus were positively associated with RV IgA seroconversion following immunization, whereas the presence of sapovirus was more common in non-seroconverters. TRIAL REGISTRATION: Clinical Trials ID: NCT03588013.