In a recent study published within the Emerging Infectious Disease journal, researchers compared the neutralization related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.5 sublineage to Omicron BA.1/BA.2 sublineages amongst vaccinated and convalescent patients.

Research Letter: Omicron BA.5 Neutralization amongst Vaccine-Boosted Individuals with Prior Omicron BA.1/BA.2 Infections. Image Credit: Jo Panuwat D / Shutterstock

Background

Since late 2021, the SARS-CoV-2 Omicron variant consistently caused a majority of infections, with over three novel subvariants that would effectively evade immunity. Within the spring of 2022, an early wave of infections resulting from the Omicron BA.1 subvariant was rapidly displaced by a wave of the BA.2 subvariant, which was subsequently replaced by the BA.5 subvariant. The BA.5 was significantly more contagious and accounted for 75% to 95% of coronavirus disease 2019 (COVID-19) cases by August 2022.

Since a big proportion of the worldwide population was infected with Omicron at the start of 2022, research is centered on whether convalescent individuals acquired natural immunity that would protect them from BA.4/BA.5 subvariants. Serum neutralization studies have shown that neither immunization nor previous infection diagnosed in the course of the early waves of Omicron infections provided sufficient protection against BA.5. Recent studies have revealed that a relatively lesser variety of BA.5-infected patients were previously diagnosed with Omicron infection, suggesting that prior Omicron infection could protect against BA.5 infection

Concerning the study

In the current study, researchers examined authentic viral neutralization capability between those that received three-dose BNT162b2 vaccination regimens to those that were immunized and later infected with SARS-CoV-2 Omicron BA.1/BA.2 subvariants.

In Odense, Denmark, the team recruited healthy individuals from the Odense University Hospital personnel and most people. 4 weeks after receiving their third BNT162b2 vaccination, serum samples were collected from the 24 members of the vaccinated cohort between 18 November 2021 and 4 February 2022. Moreover, serum samples were collected from 12 individuals from the convalescent cohort between 26 January and 19 April 2022, 4 weeks after the participants reported Omicron BA.1/BA.2 breakthrough infections.

Plaque reduction neutralization tests (PRNTs) were conducted on authentic SARS-CoV-2 Delta and Omicron BA.1, BA.2, and Ba.5 clinical isolates. The team measured PRNT90 titers, the very best serum dilution leading to greater than 90% plaque reduction. Lineages were identified via nanopore whole-genome sequencing (WGS). All serum samples were tested for spike-specific antibodies. As well as, using the Alinity SARS-CoV-2 immunoglobulin (Ig)-G assay, serum samples were evaluated for nucleocapsid-specific antibodies to find out SARS-CoV-2–naive status throughout the vaccinated group.

Results

Serum samples from the vaccinated cohort showed neutralization of Omicron BA.5 subvariant at a median PRNT90 titer of 20. In contrast, serum samples of the convalescent cohort displayed BA.5 neutralization at a median PRNT90 titer of 160. Moreover,  Wilcoxon rank-sum test indicated that this eight-fold rise in neutralization following Omicron infection had statistical significance. Moreover, the convalescent cohort displayed neutralization of SARS-CoV-2 Delta and Omicron BA.1/BA.2 subvariants at considerably higher levels than the vaccinated cohort. Within the convalescent and vaccinated groups, BA.5 neutralization was noted at median titers that were two to eight times lesser than the opposite viral strains.

Neutralization of SARS-CoV-2 variants amongst vaccine-boosted individuals with and without prior Omicron BA.1/BA.2 infections, Denmark. A) PRNT90 titers against SARS-CoV-2 Delta variant and Omicron variants BA.1, BA.2, and BA.5. B) Correlation between the degrees of spike antibodies and PRNT90 titers. Participants received 3 doses of BNT162b2 (Pfizer-BioNTech), 2 initial vaccines and a booster dose. We analyzed titers for twenty-four vaccinated participants (blue dots) who received 3 BNT162b2 doses only and 12 convalescent participants (red dots) who received 3 vaccine doses and had Omicron BA.1/BA.2 infection. For statistical evaluation, a Kruskal-Wallis test was applied initially to account for the multiple comparisons problem. Subsequently, unpaired PRNT90 titers were compared with the Wilcoxon rank-sum test, whereas paired PRNT90 titers were compared with the Wilcoxon sign rank test. Red horizontal lines indicate neutralization threshold; horizontal bars indicate median neutralization titer for every SARS-CoV-2 strain. BAU, binding antibody units; C, convalescent participant; PRNT90, plaque reduction neutralization tests with plaque reduction >90%; V, vaccinated participant.

The median concentrations of SARS-CoV-2 spike-specific antibodies varied between cohorts, with the vaccinated and convalescent cohorts having 5,535 and 5,675 binding antibody units/mL, respectively. Nonetheless, the Wilcoxon rank-sum test revealed that this variation was not statistically vital. As well as, an association was observed between the concentrations of viral spike antibodies and PRNT90 titers throughout the vaccinated cohort, while an identical relationship was not present in the convalescent group.

In response to in vitro neutralization investigations, past BA.1/BA.2 infection confers no discernible immunity against BA.5. The team evaluated two small but closely matched cohorts with comparable demographics, blood sampling intervals, and antibody levels. Infections diagnosed within the Omicron BA.1/BA.2 wave significantly improved BA.5 neutralizing capability in those receiving three-dose vaccination regimens.

Overall, the study showed that infection with Omicron BA.1/BA.2 appeared to lower susceptibility to emerging Omicron subvariants like BA.5 in individuals who received three doses of the BNT162b2 vaccination. Along side the newly reported slower decline of Omicron infection-induced immunity, the study findings suggest that prior Omicron infection significantly increases humoral protection.

Journal reference:

• Pedersen RM, Bang LL, Tornby DS, Madsen LW, Holm DK, Syndenham TV, et al., Omicron BA.5 neutralization amongst vaccine-boosted individuals with prior Omicron BA.1/BA.2 infections, Emerg Infect Dis. 2022 Dec [date cited], DOI: https://doi.org/10.3201/eid2812.221304, https://wwwnc.cdc.gov/eid/article/28/12/22-1304_article