In a recent study published on the preprint server medRxiv*, researchers investigated the differences in vaccination-induced immunities and previous infections against the Omicron BA.2 and BA.4/5 subvariants of acute respiratory syndrome coronavirus 2 severe (SARS-CoV-). 2).
Study: Higher risk of SARS-CoV-2 Omicron BA.4/5 than BA.2 infection after previous BA.1 infection, The Netherlands, May 2-July 24 of 2022. Image credit: Corona Borealis Studio/Shutterstock
background
Since November 2021, Omicron SARS-CoV-2 subvariants have increased the number of cases of coronavirus disease 2019 (COVID-19) due to their increased transmissibility and immune evasion. The Netherlands experienced an increase in cases during the dominance of the BA.1 Omicron subvariant in late 2021, followed by the subsequent periods of BA.2, BA.4 and BA.5 dominance in early to mid-2022.
Omicron subvariants have mutations in spike protein residues, resulting in increased evasion of humoral immunity. Studies have shown that the BA.4 and BA.5 subvariants have the highest degree of neutralization evasion, raising concerns about the recurrence of severe outcomes in COVID-19.
About the study
The present study examined the effect of vaccination-induced immune status and previous infection on the emergence of BA.2 and BA.4/5 between May and July 2022, the transition phase between the predominance of BA.2 and BA.4/5.
The researchers used positive test results for SARS-CoV-2 from national community testing conducted between May 2 and July 24, 2022, and conducted a spike gene targeting failure (S ) (SGTF). Pseudonymous demographic and vaccination status information was also obtained from the national community testing registry.
SGTF testing was performed using TaqPath COVID-19 real-time polymerase chain reaction (RT-PCR). Combined with quantification cycles less than or equal to 30 to amplify open reading frame 1a and ib (ORF1ab) and nucleocapsid (N) genes, failure to detect the S gene is a proxy for variants containing the S deletion 69/70, like the Omicron BA.4 and BA.5 subvariants. Non-SGTF samples were considered BA.2 positive, while SGTF samples were BA.4/5 as SGTF cannot distinguish between BA.4 and BA.5.
Whole genome sequencing (WGS) of random SGTF samples was also performed to see the ratio of BA.4 to BA.5 samples. A combination of WGS and SGTF results from previous infections was used to determine variants from previous SARS-CoV-2 infections. Immune status groups were defined according to vaccination history and previous infections. BA.2 and BA.4/5 infections were correlated with these immune status groups using various statistical analyses.
results
The results found that, regardless of vaccination status, the frequency of BA.4/5 cases was higher than BA.2 cases among individuals with previous infections, suggesting higher immune evasion by BA. 4/5 BA.2 and BA.4/5 showed no association with vaccination status, implying that the vaccines conferred equal protection against all three subvariants.
Previous infection with the BA.1 subvariant had lower and shorter protective effects against BA.4/5 than BA.2. The authors noted that a similar study from Denmark and other in vitro studies corroborated their findings that BA.1 infection-induced immunity was ineffective against BA.4/5. They also discussed studies from the United Kingdom and Portugal, which corroborate their findings of similar immunity induced by vaccination against BA.2 and BA.4/5.
However, the authors believe that the evasion shown by BA.2 and BA.4/5 from immunity induced by previous infections is less than that seen for BA.1 or the Delta variant, indicating a major escape of antibodies among the above variants of concern. that between Omicron subvariants.
The study had some limitations. Based on the lack of confidence in previous infection information, the authors believe that some people may have been misclassified as previously uninfected. Additionally, BA.4 and BA.5 infections could not be separated for the entire data set due to a lack of WGS data. In addition, the 90% threshold used for TaqPath RT-PCR testing could have resulted in misclassification of subvariants. The authors believe, however, that these limitations are unlikely to change the results significantly.
conclusion
In summary, the study found that BA.4/5 exhibits higher antibody escape than BA.2 against immunity induced by previous infections of other subvariants such as BA.1, regardless of vaccination status. Vaccination has been shown to confer uniform protection against BA.2 and BA.4/5 infections.
The findings are significant as they suggest that vaccination provides better immunity against Omicron subvariants than humoral immunity from previous infections. Therefore, vaccine updates and investigation of immune evasion by emerging subvariants should be prioritized.
*Important news
medRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, guide clinical practice/health-related behavior, or be treated as established information.