Comparison of antibody responses and vaccine effectiveness in healthcare workers post-primary COVID-19 vaccination

Since coronavirus disease 2019 (COVID-19) first emerged, it has spread to nearly every country in the world. While initially, many governments were forced to enact costly and restrictive measures to reduce the transmission of the disease, the development and mass administration of vaccines allowed many of these schemes to be dismantled. Several different vaccines were developed within a fairly short space of time, and governments give differing advice on how many doses are necessary and which vaccines to take. Researchers have investigated the effects of these vaccines on healthcare workers.

Study: Comparison of Antibody Response Durability of mRNA-1273, BNT162b2, and Ad26.COV2.S SARS-CoV-2 Vaccines in Healthcare Workers. Image Credit: lenetstan/Shutterstock

A preprint version of the study is available on the medRxiv* server while the article undergoes peer review.

The study

Participants were provided with a survey to gather information on their demographics, medical history, COVID-19 infection history, and vaccine status. Laboratory tests for the presence of anti-nucleocapsid protein antibodies confirmed infection status. Tests for both anti-spike and anti-nucleocapsid antibodies were performed using commercially available assays, while neutralization antibodies were measured using a competitive ELISA.

The researchers compared categorical variables using the chi-squared test or Fisher’s exact test with small cell sizes. Continuous variables were compared using ANOVA, although when transformations could not correct skewed data, the information was converted to ranks for analysis. A second set of analyses only covering information from mRNA-1273 vaccinated and BNT162b2 vaccinated groups included an additional dimension for certain covariates, as well as multiple linear regression. Spearman’s correlation coefficients were calculated for anti-spike protein levels and pseudoneutralization percentages.

The average age of participants was 50, and they were mostly female and white. There was an average of 0.7 comorbidities per patient. The time between the first vaccine dose and drawing of the blood was 255 days, and baseline variables were balanced by age, sex, race and comorbidities.

Individuals were split into five groups: mRNA1273-vaccinated (Group 1), BNT162b2-vaccinated (group 2), Ad26.CoV2.S-vaccinated (Group 3), the unvaccinated (Group 4), and the boosted (group 5). Group 5 showed the highest unadjusted anti-spike protein titres, while group 4 showed the lowest. Out of the vaccinated groups, group 1 performed the best, followed by 2 and then 3.

Following adjustment and multivariable analysis, the adjusted mean titres for anti-spike antibodies for groups one and two remained significant, and it was found that all covariates were independently associated with anti-spike titres except for the number of comorbidities.

A similar pattern emerged when examining the pseudo neutralization signal inhibition, with group 5 showing the highest results and group four the lowest. Similarly, group 1 outperformed group 2, which outperformed group 3. Multivariable analysis shows the time since vaccination and age were both associated with lower percentages, a finding supported by multiple other studies revealing vaccine protection wanes over time and takes hold less effectively in the elderly. Previous infection was associated with higher percentages.

The researchers also examined the infection rates among participants, which showed that anti-nucleocapsid antibodies were present at a rate of 3.4% in group 1, 3.8% in group 2, 20% in group 3, 30% in group 4 and 3.6% in group 5. However, groups 3, 4 and 5 have significantly smaller sample sizes than groups 1 and 2, with groups 3 and 4 showing ten participants each. Estimated vaccine effectivity rates were 89% for group 1, 87% for group 2, 33% in group 3 and 88% in group 5.

The scientists tried stratifying the groups by age, which showed different effects by vaccine type on anti-spike protein antibody titres and pseudo neutralization titres. Older individuals showed significantly lower responses than their younger counterparts when vaccinated with BNT162b2 but not with mRNA-1273. While stratifying by most other factors showed no difference, prior COVID-19 infection showed significant effects on titres and pseudo neutralization percentage for both vaccines.

The authors highlight that they have shown that boosted individuals are significantly more protected against SARS-CoV-2 infection than any other group, although both the mRNA-1273 and BNT162b2 vaccines also offer significant protection. The Ad26.COV2.S vaccine offers appears to offer more protection than remaining unvaccinated, but this is difficult to confirm due to low sample sizes. This information could be valuable to healthcare workers and vaccine developers and could help inform future vaccination programmes and public health policy.

*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.