Direct comparison of immune memory responses to four COVID-19 vaccines
In a recent study published in the Cellresearchers assessed host immune responses to four coronavirus disease 2019 (COVID-19) vaccines representing three different vaccine technology platforms, focusing on immune memory responses.
Researchers analyzed T cell, B cell and antibody responses to messenger ribonucleic acid (mRNA) vaccines, mRNA-1273, BNT162b2. Similarly, they analyzed the immune responses to the NVX-CoV2373 vaccine with adjuvant based on recombinant proteins and to the Ad26.COV2.S vaccine based on the viral vector.
Several preclinical trials have demonstrated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are remarkably effective in preventing progression to severe disease due to their high vaccine efficacy (VE). Likewise, population-based studies conducted under real-life conditions have shown that these vaccines have a distinct immunological mechanism of action. Therefore, the VEs of different COVID-19 vaccines for hospitalization and infection vary, with VE more stable against hospitalization over time than infection.
Studies have also established that antibodies are a strong correlate of protective immunity in the first months after vaccination. While antibodies prevent SAR-CoV-2 infection, cellular immunity modulates disease severity to resolve infection. Together, these results indicate that different COVID-19 vaccines could induce differential immune memory.
The availability of standardized cell-based assays for immunogenicity comparisons of COVID-19 vaccines is limited. More importantly, there is a lack of longitudinal studies directly assessing vaccine-specific immune memory kinetics in humans using cryopreserved peripheral blood mononuclear cells (PBMCs).
About the study
In the current study, researchers recruited and divided all study participants into four groups, with individuals in each group receiving a COVID-19 vaccine based on a different platform. Study participants were of similar gender, age, and race/ethnicity. They took blood samples from all the participants at different times and saved their plasma and PBMCs.
The team measured levels of immunoglobulin G (IgG) against the nucleocapsid (N) protein of SARS-CoV-2. In addition, they performed binding antibody and pseudovirus (pSV) neutralization assays on all test samples and measured peak (S), receptor-binding domain (RBD)-specific IgG, and anti-binding antibody. -NOT.
Finally, the researchers used correlation matrices and principal component analysis (PCA) to perform multiparametric analysis on the four vaccine platforms. In this way, they assessed the relative immunogenicity of each COVID-19 vaccine; similarly, they tested the relationship between vaccine-induced early immune responses and immune memory.
The researchers performed 1408 measurements on 352 samples to quantify pSV-binding and neutralizing antibody titers. 100% of mRNA-1273 recipients had elevated levels of S- and RBD-specific IgG and neutralizing antibodies (nAbs) six months after vaccination.
During the six months after vaccination, nAb titers tended to be lower in BNT162b2 recipients than in mRNA-1273 recipients. During the same period, the Ad26.COV2.S vaccine induced significantly lower nAb titers and IgG S and RBD than mRNA vaccine recipients, while NVX-CoV2373 recipients had nAb titers comparable to the two mRNA vaccinates.
The four different COVID-19 vaccines induced different qualities and amounts of cluster of differentiation (DC)4+ T cell, CD8+ T cell and antibody responses. All mRNA-based vaccines induced SARS-CoV-2 S-specific memory CD4 formation+ T cells and similar frequencies of S-specific memory CD8+ T cells, with circulating T follicular helper cells (cTfh) and CD4 cytotoxic T cell (CTL) populations strongly represented after vaccination with mRNA and NVX-CoV2373 vaccines. In particular, CD8+ T-cell frequencies were only detectable in 60-67% of test subjects at six months. Although antibodies produced in response to mRNA vaccines declined after six months; however, memory T and B cell populations remained relatively stable.
The researchers used S and RDB probes to identify, quantify and phenotypically characterize memory B cells from vaccinated subjects at 3.5 and 6 months post-vaccination. The kinetics of memory B cell responses to the four vaccines varied, with an observed increase in S-specific memory B cells over time. Fold increases in RBD-specific memory B cell frequencies six months after mRNA-1273, BNT162b2, Ad26.COV2.S and NVX-CoV2373 were 1.7, 2.2, 2.1 and 3.05 , respectively.
PCA mapping indicated two distinct immunological profiles for mRNA-1273 and Ad26.COV2.S vaccines, based on 3.5 and 6 months post-vaccination data. Accordingly, the distinguishing feature of the Ad26.COV2.S vaccine was that it increased the frequency of the specific chemokine receptor S 3 (CXCR3)+ memory B cells as well as natural immunity induced by infection; however, mRNA vaccines did not. The immunological profiles of the two mRNA vaccines closely resembled each other, but the profile of BNT162b2 was more heterogeneous.
The present study established the magnitude and duration of vaccine-induced immune memory across four vaccine platforms through a comprehensive assessment of effector and memory immune responses.
Of all the antigen-specific immune measures evaluated, mRNA vaccines were consistently the most immunogenic. In contrast, immune responses induced by Ad26.COV2.S were relatively weaker but more stable, and that of NVX-CoV2373 was comparable to mRNA vaccines. Data from the current study coupled with VE data for various other vaccine platforms could be relevant for other vaccination efforts.