Differential requirement of neutralizing antibodies and T cells on protective immunity to SARS-CoV-2 variants of concern

The current COVID-19 vaccines protect against severe disease, but are not effective in controlling replication of the Variants of Concern (VOCs). Here, we used the existing pre-clinical models of severe and moderate COVID-19 to evaluate the efficacy of a Spike-based DNA vaccine (pCTV-WS) for protection against different VOCs. Immunization of transgenic (K18-hACE2) mice and hamsters induced significant levels of neutralizing antibodies (nAbs) to Wuhan and Delta isolates, but not to the Gamma and Omicron variants. Nevertheless, the pCTV-WS vaccine offered significant protection to all VOCs. Consistently, protection against lung pathology and viral load to Wuhan or Delta was mediated by nAbs, whereas in the absence of nAbs, T cells controlled viral replication, disease and lethality in mice infected with either the Gamma or Omicron variants. Hence, considering the conserved nature of CD4 and CD8 T cell epitopes, we corroborate the hypothesis that induction of effector T-cells should be a main goal for new vaccines against the emergent SARS-CoV-2 VOCs.

Differential requirement of neutralizing antibodies and T cells on protective immunity to SARS-CoV-2 variants of concern.

The current COVID-19 vaccines protect against severe disease, but are not effective in controlling replication of the Variants of Concern (VOCs). Here, we used the existing pre-clinical models of severe and moderate COVID-19 to evaluate the efficacy of a Spike-based DNA vaccine (pCTV-WS) for protection against different VOCs. Immunization of transgenic (K18-hACE2) mice and hamsters induced significant levels of neutralizing antibodies (nAbs) to Wuhan and Delta isolates, but not to the Gamma and Omicron variants. Nevertheless, the pCTV-WS vaccine offered significant protection to all VOCs. Consistently, protection against lung pathology and viral load to Wuhan or Delta was mediated by nAbs, whereas in the absence of nAbs, T cells controlled viral replication, disease and lethality in mice infected with either the Gamma or Omicron variants. Hence, considering the conserved nature of CD4 and CD8 T cell epitopes, we corroborate the hypothesis that induction of effector T-cells should be a main goal for new vaccines against the emergent SARS-CoV-2 VOCs.

Profile of Brazilian inpatients with COVID-19 vaccine breakthrough infection and risk factors for unfavorable outcome.

Objective: To characterize the epidemiological and clinical profile of individuals more likely to become infected with SARS-CoV-2 after the fully vaccination schedule in order to profile priority groups to receive a booster dose in situations of vaccine doses shortage as well as for maintenance of personal protective care. Methods: This cross-sectional study used data from hospitalized COVID-19 patients aged ≥18 years, who had been fully vaccinated and had a SARS-CoV-2 infection positive diagnosis collected from the SIVEP-Gripe database (Influenza Epidemiological Surveillance Information System) from January 18, 2021 to September 15, 2021. Demographic data, clinical symptoms and preexisting medical conditions (comorbidities) were analyzed. The primary outcome was in-hospital death. Results: The majority of hospitalized patients with vaccine breakthrough infection were ≥60 years old, male, with critical or severe COVID-19. The fatality rate was extremely high (50.27%) and more pronounced in elderly groups. The most prevalent symptoms were cough, dyspnea, respiratory distress, and low blood oxygen saturation. The most frequent comorbidities were heart disease and diabetes. High fatality rates were observed among patients admitted to the intensive care units (72.88%) and those who required invasive mechanical ventilation (87.82%). The main risk factors for an unfavorable outcome were older age, respiratory compromise, inactivated virus vaccine immunization, and preexisting medical conditions. Conclusions: We characterized the profile of hospitalized Brazilian patients with COVID-19 vaccine breakthrough infection and the risk factors for an unfavorable outcome. These data allow to identify priority groups to receive a booster dose and to continue using personal protection.

Promotion of neutralizing antibody-independent immunity to wild-type and SARS-CoV-2 variants of concern using an RBD-Nucleocapsid fusion protein.

Both T cells and B cells have been shown to be generated after infection with SARS-CoV-2 yet protocols or experimental models to study one or the other are less common. Here, we generate a chimeric protein (SpiN) that comprises the receptor binding domain (RBD) from Spike (S) and the nucleocapsid (N) antigens from SARS-CoV-2. Memory CD4+ and CD8+ T cells specific for SpiN could be detected in the blood of both individuals vaccinated with Coronavac SARS-CoV-2 vaccine and COVID-19 convalescent donors. In mice, SpiN elicited a strong IFN-γ response by T cells and high levels of antibodies to the inactivated virus, but not detectable neutralizing antibodies (nAbs). Importantly, immunization of Syrian hamsters and the human Angiotensin Convertase Enzyme-2-transgenic (K18-ACE-2) mice with Poly ICLC-adjuvanted SpiN promotes robust resistance to the wild type SARS-CoV-2, as indicated by viral load, lung inflammation, clinical outcome and reduction of lethality. The protection induced by SpiN was ablated by depletion of CD4+ and CD8+ T cells and not transferred by antibodies from vaccinated mice. Finally, vaccination with SpiN also protects the K18-ACE-2 mice against infection with Delta and Omicron SARS-CoV-2 isolates. Hence, vaccine formulations that elicit effector T cells specific for the N and RBD proteins may be used to improve COVID-19 vaccines and potentially circumvent the immune escape by variants of concern.

A temporal study of Brazilian pregnant and postpartum women vulnerability for COVID-19: Characteristics, risk factors and outcomes.

BACKGROUND: During the COVID-19 second wave in Brazil, there has been a significant increase in the number of daily cases and deaths, including pregnant and postpartum women. We assess risk factors and outcomes for this priority group compared to the COVID-19 non-pregnant cohort in two epidemic waves. METHODS: In this retrospective cohort study we evaluated data of hospitalized pregnant, postpartum, and nonpregnant women aged 15-44 years, between epidemiological weeks 2020-8 and 2021-15, who tested positive for SARS-CoV-2, retrieved from the Influenza Epidemiological Surveillance Information System maintained by Ministry of Health of Brazil. We analysed in-hospital case fatality rate, crude and adjusted risk ratios on different outcomes aiming to compare data in two waves. FINDINGS: The study included pregnant women (n = 7,132), postpartum women (n = 2,405) and nonpregnant women (n = 76,278) hospitalized with COVID-19. Case fatality rates of pregnant women were lower in both waves compared to nonpregnant women, but higher among postpartum women. The risk for admission to the intensive care unit and invasive mechanical ventilation requirement in both waves was significantly higher among postpartum women compared to nonpregnant women. Cardiac disease, diabetes, obesity, and asthma were the most frequent underlying medical conditions in all patient groups. These comorbidities were significantly less frequent among pregnant women. INTERPRETATION: Pregnant women with COVID-19 are at lower risk of poor outcome compared to nonpregnant women. On the other hand, postpartum women are at higher risk of adverse outcomes compared to pregnant and nonpregnant women, especially during the second wave. There was a significant increase in the in-hospital case fatality rate for all patient groups during the second wave of COVID-19. FUNDING: This study was financed in part by CAPES, CNPq, FAPEMIG and UFSJ.