The durability of immunity and the likelihood of breakthrough infections following vaccination with four well-studied COVID-19 vaccines

In a recent study published in Proceedings of the National Academy of Sciences, researchers compared the durability of vaccine-induced immunity and natural infection against coronavirus disease 2019 (COVID-19).

Study: The durability of natural infection and vaccine-induced immunity against future infection by SARS-CoV-2. Image Credit: Numstocker/Shutterstock
Study: The durability of natural infection and vaccine-induced immunity against future infection by SARS-CoV-2. Image Credit: Numstocker/Shutterstock

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines have been proven to protect against COVID-19 disease severities for a short duration. However, various studies have reported the waning vaccine efficiency against COVID-19 infection and hospitalization. Hence, it is essential to understand the durability of immunity provided by COVID-19 vaccination to develop efficient policies to safeguard public health against COVID-19. 

About the study

In the present study, researchers used the information related to antibody response elicited by COVID-19 vaccines and their durability against breakthrough COVID-19 infections with respect to four SARS-CoV-2 vaccines, namely messenger ribonucleic acid (mRNA)-1273, BNT162b2, ChAdOx1, and Ad26.COV2.S.

The team performed analyses of waning antibody responses and breakthrough COVID-19 infection probabilities for two mRNA vaccines, including BNT162b2 and mRNA-1273, as well as two viral vector vaccines, including Ad26.COV2.S and ChAdOx1. A comparative evolutionary framework was employed to infer infection probability related to the antibody levels elicited after natural infection and the general antibody response to the four COVID-19 vaccines compared to natural infection. Furthermore, the team predicted the antibody waning profiles associated with each COVID-19 vaccine as well as infection probabilities to evaluate the probabilities of breakthrough infections.

The team also studies the phylogenetic relationships between the endemic human-infecting coronaviruses and SARS-CoV-2 based on the data obtained from 105 betacoronavirus, 58 alphacoronavirus, and 11 deltacoronavirus, and three gammacoronavirus lineages. Subsequently, maximum-likelihood molecular phylogenies were constructed by analyzing the concatenated alignment of the SARS-CoV-2 spike (S), membrane (M), and open reading frame (ORF)-1b genes.

The team further quantified the evolutionary distances between SARS-CoV-2 variants of concern such as Alpha, Beta, Delta, and Omicron and their common ancestor. This evolutionary distance was compared to the estimated evolutionary distance incident between that common ancestor and its common ancestor related to other endemic and zoonotic CoV lineages.  

Results

The study results showed that a comparison of data that estimated the peak antibody levels related to the BNT162b2 mRNA COVID-19 vaccine to that associated with natural infection resulted in nine studies providing further information for comparative analysis. These studies had 14 comparisons of the anti-receptor-binding domain (RBD), anti-S1, or anti-S immunoglobulin G (IgG) antibodies after vaccination with BNT162b2 as compared to other vaccines, including six comparisons between mRNA-1273 and BNT162b2, four between ChAdOx1 and BNT162b2, and four between Ad26.COV2.S and BNT162b2.

Quantifying the peak antibody levels observed for each COVID-19 vaccine compared to the peak antibody levels observed after natural infection using the data from the study comparisons showed that the average antibody response to both the mRNA vaccines was higher than that after natural infection. On the other hand, the average antibody response to both the viral vector vaccines was lower than that observed for the mRNA vaccines and was comparable to that after natural infection.

Ancestral- and descendent-states analysis revealed that the parameters involved in logistic regression for time-dependent reinfection probabilities highlighted the association between antibody waning profiles and reinfection or breakthrough probabilities. Breakthrough infections among mRNA-1273- or BNT162b2-vaccinated individuals were more likely to be diagnosed long after the natural infection. However, vaccination with either Ad26.COV2.S or ChAdOx1 showed probabilities of remaining free from reinfection for durations comparable to those observed after natural infections.

The team also noted that the median duration to reinfection after attaining peak antibody response against SARS-CoV-2 after infection was evaluated to be 19.2 to 32.3 months. The primary analysis showed that for the BNT162b2 and mRNA-1273 vaccines, the median duration until the incidence of a breakthrough infection was longer than that for unvaccinated natural infection. On the other hand, for the Ad26.COV2.S and ChAdOx1 vaccines, the median duration until the incidence of a breakthrough infection were 18.7 to 32.1 months and 19.9 to 32.4 months, respectively.

Conclusion

The study findings highlighted the average peak of high antibody levels expected after COVID-19 vaccination with two vaccine doses of BNT162b2 and mRNA-1273 compared to natural infection and the Ad26.COV2.S and ChAdOx1 vaccines. The researchers believe that the policymakers could use the projections concluded by the present study to develop more efficient vaccination programs to combat COVID-19 transmission.  

Journal reference:
Bhavana Kunkalikar

Written by

Bhavana Kunkalikar

Bhavana Kunkalikar is a medical writer based in Goa, India. Her academic background is in Pharmaceutical sciences and she holds a Bachelor's degree in Pharmacy. Her educational background allowed her to foster an interest in anatomical and physiological sciences. Her college project work based on ‘The manifestations and causes of sickle cell anemia’ formed the stepping stone to a life-long fascination with human pathophysiology.

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