Immune Profile and Clinical Outcome of Breakthrough Cases After Vaccination With an Inactivated SARS-CoV-2 Vaccine

Abstract

Constant efforts to prevent infections by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are actively carried out around the world. Several vaccines are currently approved for emergency use in the population, while ongoing studies continue to provide information on their safety and effectiveness. CoronaVac is an inactivated SARS-CoV-2 vaccine with a good safety and immunogenicity profile as seen in phase 1, 2, and 3 clinical trials around the world, with an effectiveness of 65.9% for symptomatic cases. Although vaccination reduces the risk of disease, infections can still occur during or after completion of the vaccination schedule (breakthrough cases). This report describes the clinical and immunological profile of vaccine breakthrough cases reported in a clinical trial in progress in Chile that is evaluating the safety, immunogenicity, and efficacy of two vaccination schedules of CoronaVac (clinicaltrials.gov NCT04651790). Out of the 2,263 fully vaccinated subjects, at end of June 2021, 45 have reported symptomatic SARS-CoV-2 infection 14 or more days after the second dose (1.99% of fully vaccinated subjects). Of the 45 breakthrough cases, 96% developed mild disease; one case developed a moderate disease; and one developed a severe disease and required mechanical ventilation. Both cases that developed moderate and severe disease were adults over 60 years old and presented comorbidities. The immune response before and after SARS-CoV-2 infection was analyzed in nine vaccine breakthrough cases, revealing that six of them exhibited circulating anti-S1-RBD IgG antibodies with neutralizing capacities after immunization, which showed a significant increase 2 and 4 weeks after symptoms onset. Two cases exhibited low circulating anti-S1-RBD IgG and almost non-existing neutralizing capacity after either vaccination or infection, although they developed a mild disease. An increase in the number of interferon-γ-secreting T cells specific for SARS-CoV-2 was detected 2 weeks after the second dose in seven cases and after symptoms onset. In conclusion, breakthrough cases were mostly mild and did not necessarily correlate with a lack of vaccine-induced immunity, suggesting that other factors, to be defined in future studies, could lead to symptomatic infection after vaccination with CoronaVac.

Safety and Non-Inferiority Evaluation of Two Immunization Schedules with an Inactivated SARS-CoV-2 Vaccine in Adults: A Randomized Clinical Trial

“…Although the study design did not allow the calculation of true efficacy for the vaccine due to the absence of a placebo arm, we demonstrate that in a scenario of high viral circulation [ 3 ], the vast majority of COVID-19 cases developed by vaccinated participants were only mild. Only two participants aged over 60 years required hospitalizations, and no deaths due to COVID-19 occurred as part of the study [ 28 ]. Accordingly, we have previously published seroconversion data for COVID-19-infected participants showing high titers of anti-RBD antibodies [ 28 ].…”

Breakthrough SARS-CoV-2 infections with the delta (B.1.617.2) variant in vaccinated patients with immune-mediated inflammatory diseases using immunosuppressants: a substudy of two prospective cohort studies

“… 6 However, severity of disease due to SARS-CoV-2 breakthrough infections and confounding risk factors for breakthrough infections were not compared between patients and controls. Other studies in healthy individuals observed associations between reduced humoral responses after SARS-CoV-2 vaccination and an increased incidence of SARS-CoV-2 breakthrough infections and possibly more severe disease, 7 , 8 , 9 but there is a paucity of data from patients with immune-mediated inflammatory diseases.…”

A booster dose of an inactivated SARS-CoV-2 vaccine increases neutralizing antibodies and T cells that recognize Delta and Omicron variants of concern

“…Furthermore, the ongoing phase 3 clinical trial in Chile has described an increase in the levels of IgG and neutralizing antibodies in adults aged 18-59 years and ≥ 60 years two- and four-weeks after the second dose of CoronaVac ® 56 . In addition, this vaccination promotes the activation of a T cell immune response against SARS-CoV-2 antigens in a 0-14 immunization schedule 5 (two-weeks interval), being an effective vaccine to prevent COVID-19 7, 8 . In Chile, 93.7% of the target population has received a first vaccine dose, and 91.4% were fully vaccinated with CoronaVac® on December 10 th of 2021 in a 0-28 days vaccination schedule 9 .…”