SARS-CoV-2 Breakthrough Infections after Third Doses Boost IgG Specific Salivary and Blood Antibodies.

SARS-CoV-2 breakthrough infections, associated with waning immunity, increase systemic antibody levels. In this study, we analyzed the impact of the infection timing on the magnitude of the systemic humoral response and whether breakthrough infections also boost antibody levels in the salivary compartment. We observed that the combination of infection plus vaccination, regardless of infection timing, produced a sharp increase in systemic antibodies, which were higher in subjects infected after third doses. Moreover, despite high systemic antibody levels, breakthrough infections after dose three occurred and boosted antibody levels in the salivary compartment. These results suggest that current vaccination strategies against COVID-19 should be improved. Results also showed that determination of salivary antibodies against SARS-CoV-2 could be a valuable tool in disease prevalence studies, for the follow-up of vaccinated individuals, and to assist vaccination strategies against COVID-19, especially in settings where blood sampling cannot be fulfilled.

COVID-19 Vaccination Responses with Different Vaccine Platforms in Patients with Inborn Errors of Immunity.

Patients with inborn errors of immunity (IEI) in Argentina were encouraged to receive licensed Sputnik, AstraZeneca, Sinopharm, Moderna, and Pfizer vaccines, even though most of the data of humoral and cellular responses combination on available vaccines comes from trials conducted in healthy individuals. We aimed to evaluate the safety and immunogenicity of the different vaccines in IEI patients in Argentina. The study cohort included adults and pediatric IEI patients (n = 118) and age-matched healthy controls (HC) (n = 37). B cell response was evaluated by measuring IgG anti-spike/receptor binding domain (S/RBD) and anti-nucleocapsid(N) antibodies by ELISA. Neutralization antibodies were also assessed with an alpha-S protein-expressing pseudo-virus assay. The T cell response was analyzed by IFN-γ secretion on S- or N-stimulated PBMC by ELISPOT and the frequency of S-specific circulating T follicular-helper cells (TFH) was evaluated by flow cytometry.No moderate/severe vaccine-associated adverse events were observed. Anti-S/RBD titers showed significant differences in both pediatric and adult IEI patients versus the age-matched HC cohort (p < 0.05). Neutralizing antibodies were also significantly lower in the patient cohort than in age-matched HC (p < 0.01). Positive S-specific IFN-γ response was observed in 84.5% of IEI patients and 82.1% presented S-specific TFH cells. Moderna vaccines, which were mainly administered in the pediatric population, elicited a stronger humoral response in IEI patients, both in antibody titer and neutralization capacity, but the cellular immune response was similar between vaccine platforms. No difference in humoral response was observed between vaccinated patients with and without previous SARS-CoV-2 infection.In conclusion, COVID-19 vaccines showed safety in IEI patients and, although immunogenicity was lower than HC, they showed specific anti-S/RBD IgG, neutralizing antibody titers, and T cell-dependent cellular immunity with IFN-γ secreting cells. These findings may guide the recommendation for a vaccination with all the available vaccines in IEI patients to prevent COVID-19 disease.

Heterologous gam-COVID-vac (sputnik V)/mRNA-1273 (moderna) vaccination induces a stronger humoral response than homologous sputnik V in a real-world data analysis.

OBJECTIVES: To compare the homologous prime-boost vaccination scheme of Gam-COVID-Vac (Sputnik V (SpV)) to its heterologous combination with mRNA-1273 (Moderna (Mod)) vaccine. METHODS: SARS-CoV-2 anti-spike (S)-receptor binding domain (RBD) IgG concentration was assessed three to seven weeks after complete vaccination. Reactogenicity was evaluated by declared side events and medical assistance required until day 7 post boost. RESULTS: Of 190 participants enrolled, 105 received homologous SpV/SpV and the remaining heterologous SpV/Mod vaccination scheme, respectively. Median (interquartile range (IQR)) age was 54 (37-63) years, 132 out of 190 (69.5%) were female, and 46 out of 190 (24.2%) individuals had a prior confirmed COVID-19. Anti-S-RBD IgG median (IQR) titers were significantly higher for SpV/Mod (2511 (1476-3992) binding antibody units (BAU)/mL) than for SpV/SpV (582 (209-1609) BAU/mL; p < 0.001] vaccination scheme. In a linear model adjusted for age, gender, time to the serological assay, and time between doses, SpV/Mod (4.154 (6.585-615.554); p < 0.001] and prior COVID (3.732 (8.641-202.010); p < 0.001) were independently associated with higher anti-S-RBD IgG values. A higher frequency of mild and moderate adverse effects was associated with the heterologous scheme (20 of 85 (23.5%) vs. 13 of 105 (12.4%); p = 0.043 and 27 of 85 (31.8%) vs. 14 of 105 (13.3%); p = 0.002), respectively, although it was well tolerated by all individuals and no medical assistance was required. DISCUSSION: The heterologous SpV/Mod combination against SARS-CoV-2 is well tolerated and significantly increases humoral immune response as compared to the homologous SpV/SpV immunization.

Humoral response to the BBIBP-CorV vaccine over time in healthcare workers with or without exposure to SARS-CoV-2.

SARS-CoV-2-specific humoral response was analyzed over time in a group of healthcare workers with or without exposure to SARS-CoV-2, who underwent vaccination with BBIBP-CorV (Sinopharm) vaccine in Argentina. Seroconversion rates in unexposed subjects after the first and second doses were 40 % and 100 %, respectively, showing a significant increase in antibody concentrations from dose 1 to dose 2 (p < 0.0001). The highest antibody concentrations were found in younger subjects and women, remaining significantly associated in a multivariable linear regression model (p = 0.005). A single dose of the BBIBP-CorV vaccine induced a strong antibody response in individuals with prior SARS-CoV-2infection, while a second dose did not increase this response. A sharp increase in antibody concentrations was observed following SARS-CoV-2 infection in those participants who became infected after the first and second doses (p = 0.008). Individuals with SARS-CoV-2 exposure prior to vaccination showed significantly higher anti-spike IgG antibody levels, at all-time points, than those not exposed (p < 0.001). Higher antibody titers were induced by a single dose in previously SARS-CoV-2 infected individuals than those induced in naïve subjects by two doses of the vaccine (p < 0.0001). Three months after the second dose both groups showed a decline in antibody levels, being more abrupt in unexposed subjects. Overall, our results showed a trend towards lower antibody concentrations over time following BBIBP-CorV vaccination. Sex and age seem to influence the magnitude of the humoral response in unexposed subjects while the combination of exposure to SARS-CoV-2 plus vaccination, whatever the sequence of the events was, produced a sharp increase in antibody levels. Evaluation of the humoral responses over time and the analysis of the induction and persistence of memory B and T cell responses, are needed to assess long-term immune protection induced by BBIBP-CorV vaccine.