As the coronavirus disease (COVID-19) pandemic continues to wreak havoc across the globe, vaccination efforts show promise in reducing transmission rates. However, the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern, with mutations at key antigenic targets, threatens the efficacy of approved vaccines.
Researchers at the Department of Viroscience, Erasmus MC, National Institute for Public Health and the Environment, Amsterdam UMC, and the Weill Medical College of Cornell University studied humoral and cellular immune responses to the wild type SARS-CoV-2, the B.1.1.7 variant (U.K. variant) and the B.1.351 variant (South African variant) in health care workers vaccinated with the BNT162b2 (Pfizer-BioNTech) mRNA vaccine.
The study, published in the journal Science Immunology, revealed that some SARS-CoV-2 variants could partially escape humoral immunity induced by infection or vaccination. Still, T cell activation is not affected by the mutations in the B.1.1.7 and the B.1.351 variants.
SARS-CoV-2 variants and immune responses
The severe acute respiratory syndrome (SARS) outbreak in 2003 was successfully contained by non-pharmaceutical interventions. However, controlling the spread of SARS-CoV-2 – a less pathogenic but more transmissible virus – has been much harder, prompting the rapid development of vaccines.
At one point or another over the course of the pandemic many countries across the world have imposed social restrictions, lockdowns, and measures to control viral spread. Some of these restrictions include school closures, home isolation, contact tracing, universal masking, and mass testing. To date, the number of cases continues to increase, reaching 170.3 million confirmed cases globally.
Only a few countries have successfully curbed SARS-CoV-2 transmission, and many countries face resurgences, caused in part by the emergence of highly transmissible new variants. Variants of concern spreading today include the B.1.1.7 (or the United Kingdom) variant; the B.1.351 (or the South African) variant; and the P.1. (or the Brazilian) variant. Two new variants have also been detected in California in February 2021, known as the B.1.427 and the B.1.429 variants.
A large part of the world depends on acquiring immunity against SARS-CoV-2 infection by vaccination and adaptive immune responses to natural infection. Though the duration of this immunity is still unclear, it provides hope that the world may attain herd immunity in the future.
Adaptive immune system
The adaptive immune response is immunity from exposure to an antigen either from a pathogen or vaccination. It is activated when the innate immune system cannot control an infection.
The fundamental components of the adaptive immune system include the B cells, CD4+ T cells, and the CD8+ T cells, which all contribute to the control of the infection.
In SARS-CoV-2 infection, the exact correlates of protection remain unclear, but it is believed that circulating antibodies and memory immune cells are crucial in protecting against COVID-19. The virus-specific neutralizing antibodies targeting the receptor-binding domain (RBD) of the spike (S) protein that coincides with the presence of SARS-CoV-2 specific CD4+ circulating follicular T cells. They can prevent the interaction between the virus and the host cell.
Further, if re-infection happens, memory B and T cells abruptly proliferate to control the infection. Subsequently, the non-neutralizing antibodies may also contribute to clearing through the Fc-receptor-mediated killing of virus-infected cells. This is termed antibody-dependent cellular cytotoxicity (ADCC).
With the emergence of variants of concern, however, it is feared that these could lead to re-infections or breakthrough infections. This could pose an efficacy threat to vaccination efforts across the globe due to the variants evading the immune system or vaccination-induced neutralizing antibodies.
S-specific CD4+ T-cell activation
In the current study, the researchers aimed to study the humoral and cellular immune responses to the wild-type SARS-CoV-2 and two variants of concern, the B.1.1.7 and the B.1.351.
The team collected serum and peripheral blood mononuclear cells (PBMC) from Pfizer-BioNTech or BNT162b2-vaccinated health care workers. They evaluated the humoral and cellular immune responses.
The study included a total of 121 healthcare workers who were vaccinated with the Pfizer-BioNTech vaccine. Of these, 23 healthcare workers recovered from mild COVID-19 and manifested a recall response with high levels of SARS-CoV-2-specific functional antibodies and virus-specific T cells after a single vaccination. However, those who were not infected with SARS-CoV-2 in the past needed two vaccinations to reach comparable levels of humoral and cellular immune responses.
The South African variant or the B.1.351 variant was less well recognized and neutralized on the antibody level. Receiving one vaccination in previously negative COVID-19 participants did not cause the emergence of cross-reactive neutralizing antibodies in most patients.
The team also noted no significant differences in CD4+ T cell responses against the wild type and the two variants of concern detected.
Overall, the study showed that in both COVID-19 recovered and those who never had COVID-19, vaccination with BNT16b2b mRNA vaccine induces potent SARS-CoV-2-specific neutralizing antibodies, CD4+ and CD8+ T cells, and ADCC-mediating antibodies.
Further, the study confirmed that a single vaccination with the BNT162b2 mRNA vaccine is adequate to induce robust immune responses in recovered patients on both the humoral and cellular levels.
Future studies are required to assess to what extent sterile immunity is a requirement to reach herd immunity and interrupt SARS-CoV-2 circulation. Continuous surveillance will monitor the incidence of breakthrough infections and duration of vaccine-induced immunity,” the researchers concluded in the study.
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