Vaccination rollouts in many countries worldwide bring hope that the coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), will eventually come to an end.
To date, over 141.12 million cases of COVID-19 have been reported globally, resulting in more than 3 million deaths. As many countries across Europe and Asia are reporting a third wave of cases, the race to vaccinate as many people as possible is on.
A team of researchers in Germany aimed to determine if the Pfizer-BioNTech vaccine mRNA vaccine (also known as the BNT162b2 vaccine) induces robust antibody responses against emergent SARS-CoV-2 variants, including the United Kingdom (or B1.1.7) variant; the South African (or B.1.351) variant; and the Brazilian (or P.1) variant.
The study, which appeared on the pre-print server medRxiv*, assessed the cellular and humoral responses against SARS-CoV-2 variants and human coronaviruses induced by the BNT162b2 vaccine.
Over the past few months, surging cases have been reported across the globe. One of the reasons why the number of cases continues to rise is due to the emergence of various variants exhibiting heightened transmissibility and increased viral fitness, including the B.1.17, B.1.351, and P.1.
As a virus replicates, its genetic code can sometimes alter under selective pressure. These changes are called mutations, and viruses with one or more new mutations are called variants of the original virus. When these variants reflect mutations that are advantageous to the virus’s spread, or exhibit more severe disease outcomes in those it infects, these are dubbed variants of concern (VoC).
The B.1.1.7 variant has a mutation in the receptor-binding domain (RBD) of the spike protein at position 501, where the amino acid asparagine (N) has been replaced with tyrosine (Y). Hence the mutation is called N501Y. Apart from this, the variant has other mutations, such as the 69/70 deletion and P681H.
The B.1.351 variant has many mutations in the spike protein, including the N501Y, E484K, and K417N.
The P.1 variant is a branch of the B.1.1.28 lineage that was first reported by the National Institute of Infectious Diseases (NIID) in Japan in travelers from Brazil. It contains the mutations K417T, E484K, and the N501Y.
Today, several vaccines encoding the viral spike (S) protein have been approved in the fight against COVID-19. Concern has mounted, however, about how effective current vaccines may be against VoCs, due to the alterations that have occurred on their antigenic targets. Further, variants B.1.351 and P.1 may resist neutralization by monoclonal antibodies (mAbs) and partial resistance to antibodies from infection or vaccination.
The results from clinical trials suggest that vaccine protection against COVID-19 starts about two weeks after the first dose. Only modest neutralization activity of sera was seen shortly before the second vaccine dose, and a strong increase in neutralizing antibody titers needed a second boosting dose.
Due to the increasing number of cases and the limited supply of vaccines, the UK’s Joint Committee on Vaccines and Immunization proposed extending the time in receiving the second dose. This way, more people would receive the first dose within a short period.
Assessing whether delaying the second dose may cause a short-lived or incomplete anti-SARS-CoV-2 immunity and other associated risks is crucial.
To assess its effectiveness against VoCs, the researchers analyzed cellular and humoral immune responses induced by the primer and booster doses of the Pfizer-BioNTech (BNT162b2) COVID-19 vaccine. The team also determined the impact of preexisting immunity against human coronavirus.
The team assessed humoral and T cell responses against SARS-CoV-2 wild type and variants of concern, including endemic human coronaviruses (hCoVs) that were stimulated after single and double vaccination with the BNT162b2 vaccine.
They also determined the anti-SARS-CoV-2 S immunoglobulin G (IgG) and immunoglobulin A (IgA) levels in individuals early (8.7 days) and late (20.6 days) after immunization with a single 30 µg dose of BNT162b2. Further, samples collected at 21 days after a second dose were analyzed.
The team found that antibodies of the IgG subtype against the S1 subunit of SARS-CoV-2 S were detected at about 14 days after the first vaccine dose, with almost all the participants having measurable IgG levels 17 days after the first Pfizer-BioNTech dose.
Meanwhile, the team detected anti-SARS-CoV-2 IgA in all the participants at an average of 20.2 days, with a range of 19 to 25 days, after the first dose. The magnitude of the anti-SARS-CoV-2 IgG antibody response was markedly higher 21 days after the second Pfizer-BioNTech vaccine dose.
However, when testing plasma samples in a surrogate virus neutralization test, a similar scenario emerged. Most plasma samples between days two and 14 after the first vaccine dose remained below the cut-off of the assay, which was 30 percent. On the other hand, almost all the participants had SARS-CoV-2 S1 RBD inhibitory antibodies detectable beyond 17 days after the first vaccine dose.
To further assess the inhibitory activity of plasma samples 17 to 21 days after the first BNT162b2 dose, the team diluted plasma with more than 50 percent inhibition in the Surrogate Virus Neutralization Test (sVNT) and compared the results to those from convalescent COVID-19 patients or people 21 days after the second vaccine dose.
The plasma samples with inhibitory activity less than 90 percent at the highest plasma concentration demonstrated a rapid and linear decline by dilution. Only samples with baseline inhibition of more than 90 percent maintained over 50 percent inhibition in the sVNT upon further dilution. This means that there are low body antibody concentrations in most plasma samples.
The findings suggest that SARS-CoV-2 needs little affinity maturation and can be detected in the plasma at 10 to 14 days after the first vaccine dose.
Will a single BNT162b2 vaccine induce antibodies?
To determine whether a single BNT162b2 vaccine dose inhibits host cell entry driven by wild-type S protein and the S proteins of the three viral variants, the team used a VSV-based vector pseudotyped virus for each. The plasma collected from patients with severe and current COVID-19 due to the wild-type was included as the control.
The team found that the plasma samples effectively reduced entry of the wild-type virus and the S protein of variant B.1.1.7 variant. On the other hand, the vaccine was less effective in blocking the viral entry of the B.1.351 and P.1 variants.
Similar results emerged from the plasma collected from vaccinated individuals 21 days after the second vaccine dose. The Pfizer-BioNTech vaccine effectively neutralized viral entry driven by the wild-type S protein. Yet, it was less efficient in inhibiting entry driven by the B.1.1.7 variant or the U.K. variant.
Overall, the team found that a single dose of the BNT162b2 vaccine might frequently fail to induce an adequate neutralizing antibody response. Even if it does trigger an immune response, it may not be as effective on the B.1.351 variant or the South African variant.
T cell immunity
To evaluate T cell immunity after receiving the vaccine, the researchers assessed the frequencies of T cells producing interferon-gamma (IFN) when stimulated with peptide pools obtained from the S protein of SARS-CoV-2 and other human coronaviruses, like hCoV-OC43 and hCoV-299E, and the cytomegalus virus (CMV) pp65, which was the control.
The team found that the T cells reactive to peptide stimulation from SARS-CoV-2 wild-type, B.1.1.7, and B.1.351 were not detected in more than 40 percent of individuals who received their first vaccine dose. However, T cell levels significantly increased after boosting.
The team also observed markedly increased IFN production by PBMCs after the first and second vaccine doses.
Taken together, our data are in line with our previous analyses in convalescent COVID-19 patients and show that the magnitude of B and T cell responses against SARS-CoV-2 upon vaccination is wide-ranging and differs for distinct virus variants,” the researchers explained in the study.
“Particularly, the magnitude of SARS-CoV-2-specific T cell responses shows great heterogeneity and is not readily detectable after a single shot,” the team added.
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.