Vaccination and BA.1 breakthrough infection induce neutralizing antibodies less efficient against BA.4 and BA.5 Omicron variants

By Nidhi Saha, BDSReviewed by Aimee MolineuxAug 2 2022

A recent study published in the Eurosurveillance journal aimed to describe the appearance of the Omicron variants in Israel, from March to June 2022, as well as the neutralizing antibody response against the primary Omicron subvariants.

Background

The Omicron variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains the dominant variant of concern (VOC) as of July 2022. Characteristic features of infection with Omicron variants are high transmissibility, mild symptoms, immune evasion, and lower susceptibility to monoclonal antibodies therapy. 

The Omicron variants were categorized into four main sub-variants, namely, BA.1, BA.2, BA.4, and BA.5, which harbor greater than 30 mutations in their spike (S) proteins when compared to the prior Alpha and Delta variants. While the BA.4 and BA.5 have three additional mutations in their S proteins compared to the BA.2, this is likely to heighten the immune-evasion capabilities and resilience of these variants.

Methods

In Israel, 49,810 genome sequences of SARS-CoV-2 variants BA.1, BA.2, BA.4, and BA.5 were analyzed between March-June 2022. The BA.2 mutant was found to be the most dominant through most of this duration. The country first documented BA.4 and BA.5 variants’ occurrence in mid-April 2022; however, BA.5 was detected more frequently than BA.4 in early June 2022. 

This study evaluated neutralizing antibodies against the wild-type (WT) sub-lineage B.1.1.50, as well as the Omicron variants (BA.1, BA.2, BA.4, and BA.5) among healthcare workers (HCW) who had BA.1 infection. All the 41 HCWs selected did not have a history of infection with other SARS-CoV-2 variants.

The participants were divided into various cohorts – group 1 comprised 11 unvaccinated HCWs, wherefrom sera were obtained one month after the BA.1 infection; group 2 had 15 three times Comirnaty-vaccinated HCWs – sera were obtained five months after the third dose; and group 3 comprised 15, three times vaccinated HCWs (Comirnaty vaccine) who had a breakthrough infection with BA.1 – sera were extracted one month later.

Hereafter, group 2 was administered the fourth dose, and sera were obtained one month later. This group evidenced breakthrough infection with Omicron BA.1 and sera were derived after one month. The geometric mean titers (GMTs) of these groups were compared.

Results

It was observed that the Omicron BA.1 infection induced a comparatively lower neutralization efficiency against BA.1 and BA.2 in unvaccinated HCWs. However, effective neutralization against BA.4, BA.5, or WT seemed insignificant.

The neutralization efficiency of the antibodies collected from HCWs with three vaccine doses against the WT strain was markedly higher than those derived from samples from group 1. While after the breakthrough infection, the neutralization efficiency against the WT strain, as well as that against various Omicron variants, was heightened.

Notably, the baseline neutralization efficiency of those immunized four times was much higher than that of HCWs vaccinated three times. After the breakthrough infection, neutralization potential against the WT strain and different Omicron variants rose significantly.

However, the neutralization potential against the BA.5 strain remained the lowest, even among the participants infected with BA.1 after three or four vaccine doses. Meanwhile, the neutralization potential against the WT strain was greater after four Comirnaty vaccine doses than three. On the other hand, neutralization efficiency against BA.4 and BA.5 was equivalent among HCWs vaccinated three or four times.

Moreover, neutralization efficiency against all Omicron variants was considerably higher among participants vaccinated before the BA.1 infection than unvaccinated convalescent individuals. The neutralization potential against BA.5 was the lowest in all HCWs and those against the WT strain were higher than against Omicron variants.

Of note, the duration of time elapsed after the third dose was greater than that after the fourth dose vaccination, and hence, the data varies. Yet, Omicron neutralization appeared to match between the two recipient groups.

Conclusion

The findings depicted low neutralization efficiency of sera obtained from BA.1 convalescent individuals vaccinated with three or four Comirnaty vaccine doses, against BA.4 and BA.5. Thus, Omicron-specific vaccination may be warranted to combat the ongoing dominant VOC instrumental in the sustenance of the ongoing coronavirus disease 2019 (COVID-19) pandemic.