In a recent study published in the journal Emerging Infectious Disease, researchers compared neutralization associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.5 sublineage with Omicron BA.1/BA.2 sublineages between vaccinated and convalescent. patients
Research Letter: Neutralization of Omicron BA.5 among vaccine-boosted individuals with prior Omicron BA.1/BA.2 infections. Image credit: Jo Panuwat D / Shutterstock
background
Since late 2021, the Omicron SARS-CoV-2 variant consistently caused the most infections, with more than three new subvariants that could effectively evade immunity. In the spring of 2022, an early wave of infections due to the Omicron BA.1 subvariant was quickly displaced by a wave of the BA.2 subvariant, which was later replaced by the BA.5 subvariant. BA.5 was significantly more contagious and accounted for 75% to 95% of cases of coronavirus disease 2019 (COVID-19) in August 2022.
Since a significant proportion of the world’s population became infected with Omicron in early 2022, research is focused on whether convalescent individuals acquired natural immunity that could protect them from the BA.4/BA.5 subvariants. Serum neutralization studies have shown that neither immunization nor previous infection diagnosed during the first waves of Omicron infections provided sufficient protection against BA.5. Recent studies have revealed that a comparatively smaller number of BA.5-infected patients were previously diagnosed with Omicron infection, suggesting that prior Omicron infection might protect against BA.5 infection.
About the study
In the present study, the investigators examined true viral neutralization capacity among those who received three-dose BNT162b2 vaccination regimens and those who were immunized and subsequently infected with Omicron BA.1/BA.2 SARS-CoV subvariants -2.
In Odense, Denmark, the team recruited healthy individuals from staff at Odense University Hospital and the general public. Four weeks after receiving their third BNT162b2 vaccination, serum samples were collected from 24 members of the vaccinated cohort between November 18, 2021 and February 4, 2022. In addition, serum samples were collected from 12 individuals in the convalescent cohort between January 26 and April 19, 2022. , four weeks after participants reported breakthrough Omicron BA.1/BA.2 infections.
Plaque reduction neutralization tests (PRNT) were performed on authentic clinical isolates of SARS-CoV-2 Delta and Omicron BA.1, BA.2 and Ba.5. The team measured PRNT90 titers, the highest serum dilution that resulted in more than 90% plaque reduction. Lineages were identified by nanopore whole genome sequencing (WGS). All serum samples were tested for spike-specific antibodies. In addition, using the Alinity SARS-CoV-2 immunoglobulin (Ig)-G assay, serum samples were assessed for nucleocapsid-specific antibodies to determine the naïve status of SARS-CoV-2 within of the vaccinated group.
results
Serum samples from the vaccinated cohort showed neutralization of the Omicron BA.5 subvariant with a mean PRNT90 titer of 20. In contrast, serum samples from the convalescent cohort showed neutralization of BA.5 with a mean PRNT90 titer of 160. Furthermore, the Wilcoxon rank sum test indicated that this eightfold increase in neutralization after Omicron infection was statistically significant. In addition, the convalescent cohort showed neutralization of SARS-CoV-2 Delta and Omicron BA.1/BA.2 subvariants at considerably higher levels than the vaccinated cohort. In the convalescent and vaccinated groups, neutralization of BA.5 was observed with mean titers that were two to eight times lower than the other viral strains.
Neutralization of SARS-CoV-2 variants among vaccine-boosted individuals with and without previous Omicron BA.1/BA.2 infections, Denmark. A) PRNT90 titers against the Delta variant of SARS-CoV-2 and the Omicron variants BA.1, BA.2 and BA.5. B) Correlation between spike antibody levels and PRNT90 titers. Participants received 3 doses of BNT162b2 (Pfizer-BioNTech), 2 prime vaccines and a booster dose. We analyzed the titers of 24 vaccinated participants (blue dots) who received only 3 doses of BNT162b2 and 12 convalescent participants (red dots) who received 3 doses of vaccine and had Omicron BA.1/BA.2 infection. For statistical analysis, a Kruskal-Wallis test was initially applied to account for the problem of multiple comparisons. Unpaired PRNT90 titers were subsequently compared with the Wilcoxon rank-sum test, while paired PRNT90 titers were compared with the Wilcoxon signed-rank test. The red horizontal lines indicate the neutralization threshold; horizontal bars indicate the mean neutralization titer for each SARS-CoV-2 strain. BAU, binding antibody units; C, convalescent participant; PRNT90, plaque reduction neutralization tests with >90% plaque reduction; V, vaccinated participant.
Median SARS-CoV-2 spike-specific antibody concentrations varied between cohorts, with the vaccinated and convalescent cohorts having 5,535 and 5,675 binding antibody units/ml, respectively. However, the Wilcoxon rank sum test revealed that this variation was not statistically significant. Furthermore, an association was observed between viral spike antibody concentrations and PRNT90 titers within the vaccinated cohort, whereas a similar relationship was not found in the convalescent group.
According to in vitro neutralization studies, prior infection with BA.1/BA.2 does not confer detectable immunity against BA.5. The team evaluated two small but highly matched cohorts with comparable demographics, blood sampling intervals and antibody levels. Infections diagnosed in the Omicron BA.1/BA.2 wave significantly enhanced the neutralizing capacity of BA.5 in those receiving three-dose vaccination regimens.
Overall, the study showed that infection with Omicron BA.1/BA.2 appeared to reduce susceptibility to emerging Omicron subvariants such as BA.5 in individuals who received three doses of the BNT162b2 vaccine. Together with the slower decline in immunity induced by Omicron infection, the results of the study 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., Neutralization of Omicron BA.5 among vaccine-boosted individuals with prior Omicron BA.1/BA.2 infections, Emerg Infect Dis. December 2022 [date cited]DOI: