Vaccination amps up antibody response and cuts down COVID severity, UK study shows

In a recent article posted to the medRxiv* preprint server, researchers evaluated the serological outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among coronavirus disease 2019 (COVID-19) vaccinated and unvaccinated individuals in England during the Alpha, Delta, and Omicron waves spanning the period between February 2021 and April 2022.

They used prospective data collected through the enhanced surveillance system (ES) set up in 2021 by the United Kingdom Health Security Agency (UKHSA) to monitor the incidence of COVID-19 in vaccinated individuals.

Study: Serological outcomes of SARS-CoV-2 infection by vaccination status and variant in England. Image Credit: Mongkolchon Akesin / Shutterstock

*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Background

Similar to the SARS-CoV-2 transmission pattern worldwide, in England, each variant had a distinct time of predominance; for instance, Alpha was the predominant variant before May 2021, while Delta dominated between May and November 2021. The Delta variant caused more severe infections and was highly transmissible, yet Omicron emerged and replaced Delta as the predominant variant from December 2021 onward.

Given the varying severity and immune profiles of all SARS-CoV-2 variants, vaccines rolled out to prevent COVID-19 elicited varying immune responses, necessitating investigations of serological outcomes or the antibody response to SARS-CoV-2 infection stratified by vaccination status, vaccine type, and infecting variant among the general population of England.

In the UK, they used messenger ribonucleic acid (mRNA) and adenoviral vector vaccines for primary vaccination and only mRNA vaccines for booster vaccinations. 

To date, scientific evidence of the antibody response post-infection has remained focused on specific populations, e.g., healthcare professionals. Nonetheless, studies consistently found that the effectiveness of SARS-CoV-2 vaccines waned over time, and individuals who contracted COVID-19 developed a quicker and more persistent response to COVID-19 vaccines than naive individuals. 

However, the effect of antibody responses on the risk of developing severe COVID-19 by vaccine type, vaccination status, and infecting variant requires further investigation. This data could inform future vaccination strategies and design more effective next-generation COVID-19 vaccines for the future. 

About the study

In the present study, UKSHA nurses contacted all eligible individuals at and post-recruitment to collect information on their demographics, COVID-19 illness symptoms, symptoms type, symptom severity, symptoms onset date, exposure risk factors, and comorbidities. They sent them self-sampling kits, using which the study participants provided nasal/oropharyngeal swabs on days 1/3/7 post-recruitment, plus acute and convalescent serum samples and oral fluid samples.

All eligible individuals were English residents aged ≥18 years, SARS-CoV-2-reverse transcription polymerase chain reaction (RT-PCR)-positive, and vaccine-eligible at enrollment into the study.

The team tested serum samples for antibodies against SARS-CoV-2 spike (S) and nucleoprotein (N) using distinct electrochemiluminescence immunoassays; likewise, oral fluid for SARS-COV-2 anti-N and anti-S antibodies. 

The RT-PCR cycle threshold (C_T) value indicated SARS-CoV-2 viral load, and whole-genome sequencing (WGS) confirmed the variant status of SARS-CoV-2-positive RT-PCR swabs. The study analysis covered data from individuals with qualitative acute or convalescent antibody results.

Further, the researchers performed multivariable logistic regression analysis to examine the seroconversion status of anti-N antibodies from negative to positive, adjusting for self-reported age, sex, ethnicity, comorbidities, time since the event, and clinically extremely vulnerable (CEV) and immunosuppressed status. In addition, they estimated the convalescent anti-N and anti-S antibody geometric levels, stratifying results for both by vaccination status and infecting the SARS-CoV-2 variant. 

Furthermore, the researchers performed multivariable linear regression analysis to estimate the anti-S antibody geometric mean levels in acute sera by vaccine type and interval-censored survival analysis to examine the effect of anti-S antibody levels in acute sera on the duration of RT-PCR positivity.

Finally, they evaluated the effect of anti-S antibody levels in acute sera on the number of symptoms (1-5 versus ≥6 symptoms) using the multivariable logistic regression model and the same variables used for other analyses.

Results

The analytical set of the current study comprised 1,497 RT-PCR-positive individuals with an average age of 49 years who had different vaccination statuses and contracted infection from different SARS-CoV-2 variants. 

Convalescent and acute serum and oral fluid samples for 1,115 individuals were available, of which 1,065 (95.5%) samples showed seroconversion. After SARS-CoV-2 infection, convalescent anti-N and anti-S antibody levels were lower and higher in vaccinated individuals. Notably, the baseline to convalescent anti-N antibody levels ratio was higher for unvaccinated versus vaccinated individuals; perhaps infection in vaccinated individuals was milder and did not provoke a robust anti-N antibody response. 

Moreover, convalescent anti-N antibody levels did not significantly vary by the presence of comorbidities but varied with gender, age, and ethnicity. Thus, convalescent anti-N antibody levels were higher against the Delta variant for other ethnic groups than white.

In acute sera, the anti-S antibody level tended to be greater for mRNA versus adenoviral vector vaccines but did not vary by study variables. Moreover, as anticipated, the acute anti-S antibody level surged with the number of vaccine doses received.

Compared to individuals with 1,000-9,999 antibody units (AU)/ml antibody level overall, those with ≥10,000 AU/ml anti-S antibody levels had a significantly shorter duration of RT-PCR positivity; in addition, they had higher viral loads, as indicated by their significantly lower C_T values. 

Previous studies have established antibody levels as correlates of immune protection; in agreement, the present study findings suggested that those with higher antibody levels may develop milder illness and rapidly clear the infection. Furthermore, individuals with higher acute anti-S antibody levels were less likely to develop six or more symptoms overall, especially for the Delta variant. Immunosuppressed and CEV individuals, in general, mounted a lower antibody response.

Conclusions

The current study data adds to the real-world evidence that COVID-19 vaccination effectively reduces COVID-19 symptoms and their severity following infection. Post-SARS-CoV-2 infection, vaccination increased convalescent anti-S antibody levels and decreased convalescent anti-N antibody levels. 

More importantly, the association between high acute anti-S antibody levels and reduction in the duration of positivity and increased CT values suggested a lower risk of onward transmission of SARS-CoV-2 due to vaccination. Overall, the current study findings further the understanding of antibody response(s) following COVID-19, stratified by vaccination status and infecting variant.

*Important notice: 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.

Written by

Neha Mathur

Neha is a digital marketing professional based in Gurugram, India. She has a Master’s degree from the University of Rajasthan with a specialization in Biotechnology in 2008. She has experience in pre-clinical research as part of her research project in The Department of Toxicology at the prestigious Central Drug Research Institute (CDRI), Lucknow, India. She also holds a certification in C++ programming.