Possible influence of anti-vector immunity and SARS-CoV-2 variants on efficacy of ChAdOx1 nCoV-19 vaccine and the proposal of a new pharmacotherapy

Abstract

The present work analyses in detail the published data on ChAdOx1 nCoV-19 vaccine and provides arguments for the involvement of anti-vector immunity and of SARS-CoV-2 variants on the efficacy of ChAdOx1 nCoV-19 vaccine. First, it is suggested that anti-vector immunity takes place as the regimen of homologous vaccination with ChAdOx1 nCoV-19 vaccine is applied and interferes with efficacy of the vaccine when the interval between prime and boost doses is less than three months. Second, longitudinal studies suggest that ChAdOx1 nCoV-19 vaccine provides sub-optimal efficacy against UK variant of SARS-CoV-2, which appears to have an increased transmissibility over the ancestral SARS-CoV-2 among vaccinated people. At the moment, ChAdOx1 nCoV-19 vaccine is able to reduce the severity of symptoms and transmissibility; however, if the vaccinated individuals do not maintain everyday preventive actions, they could turn into potential spreaders, thus accelerating the process of generation of new viral variants due to the selective pressure of immune response. Prediction and possible consequences of the SARS-CoV-2 evolution and repeated anti-SARS-CoV-2 vaccinations are discussed. Since the impact of emerging SARS-CoV-2 variants suggests that vaccines are unlikely to be effective in quickly solving the pandemic crisis, it is highlighted the need to keep searching for new and more efficacious pharmacotherapy for COVID-19, such as those targeting ACE2 and ADAM17 zinc-metalloprotease activities.

Kinetics of the Antibody Response to Boostering With Three Different Vaccines Against SARS-CoV-2

“…One explanation for this difference might be found in the possibility of immune responses against the adenoviral vector impairing the induction of the desired immune response to the vaccine. While the use of a chimpanzee adenoviral vector all but precludes the possibility of preexisting immunity against the vector of ChAdOx ( 17 ), the reutilization of the same vector for the second dose might give rise to antivector immunity that interferes with vaccine delivery ( 18 ). Other manufacturers have employed different adenoviral vectors for prime and boost doses to circumvent this phenomenon ( 19 , 20 ).…”