Study suggests an immunological benefit of combining previous natural infection with vaccination against COVID-19 using a combination of different vaccine platforms

In a recent study published in PLoS Pathogens, researchers explored severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-targeted immune responses among COVAC1 participants who received a novel self-amplifying ribonucleic acid (saRNA) vaccine followed by the messenger RNA (mRNA) BNT162b2 vaccine BNT162b2 vaccine, with or without prior coronavirus disease 2019 (COVID-19) history.

Study: Enhanced immune responses following heterologous vaccination with self-amplifying RNA and mRNA COVID-19 vaccines. Image Credit: ezps/Shutterstock
Study: Enhanced immune responses following heterologous vaccination with self-amplifying RNA and mRNA COVID-19 vaccines. Image Credit: ezps/Shutterstock

Background

Vaccination strategies to boost pre-existing humoral and cell-mediated immune responses to SARS-CoV-2 must be optimized to improve global public health. The continual emergence of novel SARS-CoV-2 variants of concern (VOCs) has threatened vaccine efficacy and immune levels among individuals with prior COVID-19 history, those who received COVID-19 vaccinations, or both (hybrid immunity). Even though vaccination strategies are yet to be optimized, studies have reported enhanced immune protection from booster dose administrations and vaccinations following natural SARS-CoV-2 infections.

About the study

In the present study, researchers compared immune responses among COVAC1 participants who received two saRNA vaccine doses and subsequently a BNT162b2 vaccine dose (heterologous vaccination) and those who were administered BNT162b2 mRNA vaccine doses only (homologous vaccination).

Thirty-five individuals who received saRNA in the COVAC1 trial and 40 individuals who received only BNT162b2 homologous vaccinations (non-saRNA vaccine group) were enrolled for the analysis. The saRNA vaccinees also received mRNA BNT162b2 (n=25) or ChAdOx nCoV-19 adenoviral vector (n=10) vaccinations.

Among the heterologous and homologous vaccinees, 15 and 18 individuals reported prior COVID-19 history, respectively, confirmed by reverse transcription-polymerase chain reaction (PCR) or diagnostic antibody (Ab) testing. Binding Ab (bAb) titers against SARS-CoV-2 spike (S), and nucleocapsid (N) proteins were assessed by enzyme-linked immunosorbent assay (ELISA) assays.

Neutralizing Ab (nAb) titers against the SARS-CoV-2 wildtype (WT) strain and Delta VOC and Omicron VOC were assessed using pseudovirus (PV)-based neutralization assays and human embryonic kidney (HEK)293T-ACE2 (angiotensin-converting enzyme 2) cells. Geometric mean titers (GMT) and 50% neutralization titers (NT50) were evaluated. Cell-mediated immune responses were monitored using AIM (activation-induced marker) assays and IFN-γ (interferon-gamma) release assays.

Results

Fifty percent of the participants in both groups showed COVID-19 recovery with greater humoral Ab-mediated and cellular T lymphocyte-mediated immune responses among those with prior COVID-19 history and individuals who were administered heterologous vaccinations. Most (83%) participants who were SARS-CoV-2-naïve and received saRNA vaccinations showed seroconversion after the second vaccination, and individuals with prior COVID-19 history showed 27-fold greater Ab titers 14 days after the heterologous saRNA vaccinations.

However, Ab titers were lesser than those observed post-homologous mRNA vaccinations. After 14 days of the second mRNA vaccination, the bAb and nAb titers were statistically significantly greater among heterologous vaccinees with prior COVID-19 history compared to homologous vaccinees or SARS-CoV-2-naive participants.

Cellular immune responses were also greatest among heterologous vaccines with prior COVID-19 history, with a greater fraction of anti-S cluster of differentiation (CD)8+ (natural killer T lymphocytes) compared to CD4+ (or helper) T lymphocytes in comparison to homologous mRNA vaccinees. The findings indicated an immune advantage of greater SARS-CoV-2 exposure, from previous natural SARS-CoV-2 infections and SARS-CoV-2 vaccinations, especially among heterologous mRNA and saRNA vaccinees.

Neutralization against VOCs was best maintained among previously-infected heterologous vaccinees. However, the findings were significant only for Omicron BA.4/5. Cross-neutralization against Delta and Omicron VOCs was lower among homologous vaccinees than heterologous vaccinees, although significant only for BA.4/5 (40-fold decrease versus 22-fold).

Heterologous vs. homologous vaccinees showed neutralization titer decreases of three-fold vs. five-fold for Delta, seven-fold vs. 11-fold for BA.1, and 22-fold vs. 43-fold for BA.4/5). The greatest CD8+ T-lymphocyte responses were observed among previously-infected heterologous vaccinees 14 days after the second mRNA dose than those without previous infection and for infected or uninfected homologous vaccinees (GM O.5% vs. 0.2% vs. <0.1%).

Of COVAC1 saRNA SARS-CoV-2-naïve vaccinees, nAb titers against WT were detected in 67% of individuals 14 days following the second saRNA vaccination (NT50 57), and following the second mRNA vaccination, a 20-fold increase was observed. Among previously-infected saRNA vaccinees, a baseline GM NT50 of 107 was observed, which increased by four-fold and seven-fold 14 days after the second saRNA dose and the second mRNA dose, respectively.

The bAb and nAb titer positively correlated with each other, with the least correlation regarding BA.4/5 neutralization. No correlations were observed between the Ab titers against time from SARS-CoV-2 infection to the initial vaccination. SARS-CoV-2 antigen-targeted cellular T lymphocyte responses correlated positively with IFN-γ release and humoral Ab titers, with a significant correlation between bAb and IFN-γ release.

Conclusion

Overall, the study findings showed an immunological benefit of hybrid immunity from previous natural infections and heterologous saRNA and mRNA vaccinations against SARS-CoV-2.

Journal reference:
Pooja Toshniwal Paharia

Written by

Pooja Toshniwal Paharia

Dr. based clinical-radiological diagnosis and management of oral lesions and conditions and associated maxillofacial disorders.

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Comments

  1. Larry Jason Carter Larry Jason Carter United States says:

    This is very misleading. It doesn't take this person and the natural immunity after hybrid approach and see what it's like given a year. We know the vaccine based on how it works causes an over production of plasma cells.

    It also looks at this without taking in account a T response. We know some people can take care of it purely from a T response so show no symptoms. Just a really flawed and misleading paper.

  2. Daniel O'Keefe Daniel O'Keefe United States says:

    Very surprised this suggested "previous" "natural immunity" or previous infection but in fact isn't really. Study did not study those previously infected and NOT vaccinated. Why not? Isn't that the baseline? Isn't that the opposite of Covid Naive?

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