• Timing of vaccination may influence new Omicron ‘Breakthrough Infection’ outbreak
• Omicron infection induces higher neutralizing antibodies following a breakthrough infection

SARS-CoV-2 is a virus that causes considerable morbidity and mortality all around the world.

In the wake of the discovery of a novel SARS-CoV-2 strain known as Omicron belonging to the Pango lineage B.1.1.529, outbreaks have expanded swiftly throughout the world, particularly in the United States, the UK and Asia.

In response to possible changes in viral properties, the World Health Organization (WHO) categorized SARS-CoV-2 variant B.1.1.529 as a Variant of Concern (VOC).

This new VOC has more mutations in its spikes than earlier VOCs, posing serious concerns for worldwide public health. COVID-19 vaccinations, on the other hand, continue to be the most effective means of protecting against the SARS-CoV-2 virus and its variants of concern.

After receiving full COVID-19 vaccination, a person infected with SARS-CoV-2 is a breakthrough case. However, as no vaccination can offer 100 percent protection against outbreaks of illness in all patients who receive it, the occurrence of this is expected to occur in a small number of those who receive it. According to this research, breakthrough infections that occur after immunization may actually serve to protect against other strains of concern.

The findings, which have been posted on the preprint medRxiv* server and are pending peer review, reveal that the timing of Omicron infections following immunization is a crucial factor driving outbreaks.

Effective or cross-reactive neutralizing antibodies that neutralize Omicron following Alpha or Delta breakthrough infections were induced by the time between vaccination and breakthrough infections.

In their new study, the researchers looked at neutralizing antibody activity in plasma samples from 20 healthcare professionals who had received two doses of the Pfizer-BioNTech COVID-19 vaccine, which was designed to protect against different SARS-CoV-2 strains. The samples were collected 52 days and 171 days following the second treatment, respectively.

Using both pseudovirus-based and live-virus neutralization assays, immune responses against the viruses Beta, Delta, and Omicron were assessed. Historically, the SARS-CoV-2 Pango lineage A strain was used as a reference for ancestors.

The results revealed that the Omicron variant resulted in a considerable decrease in the neutralizing activity of fully vaccinated people ranging from 3- to 8-fold. In particular, practically all samples tested negative for neutralizing action against Omicron. In comparison to the Beta and Delta variants, the loss of neutralizing activity with Omicron was significantly greater.

Previous research indicates that a two-dose vaccine increased immune responses, which effectively neutralized additional SARS-CoV-2 strains. In this study, the researchers looked to see if the same thing happened with Omicron.

In this study, the researchers looked at convalescent serum samples from vaccinated patients who developed breakthrough Alpha or Delta infections – around half of the illnesses were caused by Delta, which occurred later in the Alpha outbreak and 60 days or more after vaccination.

When compared to the original SARS-CoV-2 strain, they discovered a significant increase in neutralizing activity against Delta. Individuals who had previously been infected with the Delta variant exhibited the highest levels of neutralization against Delta virus.

This concludes “breakthrough infection preferentially induces antibodies with high neutralizing activity against the infected variant.”

When exposed to Beta, neutralizing activity was found to be reduced by a factor of 3.8. Furthermore, Omicron decreased neutralizing activity by a factor of 9.7. According to the results of a live-virus neutralization assay, two isolated samples of the Omicron strain had much lower neutralizing activity than the original strain by nearly tenfold.

In contrast to neutralizing activity in the vaccinated-only cohort, the researchers discovered that there were significant individual differences in the extent of reduction in neutralizing activity within the vaccinated-only cohort. In certain cases, cross-neutralizing action was observed in serum samples from people who had been vaccinated but had developed breakthrough infections. Furthermore, cross-neutralization was found to be effective against Omicron at a level comparable to that observed with previous SARS-CoV-2 variants.

The Omicron strain had a stronger capacity for cross-neutralization following a breakthrough infection, whereas the Delta variant had a lower potential for cross-neutralization.

Increases in neutralizing activity against each variant, including Omicron, were observed in direct proportion to the length of time between immunization and infection.

The Beta and Omicron variants showed the highest correlation between neutralizing activity and vaccination-to-infection.

However, the trend was different when it came to neutralizing Delta activity after a Delta-caused breakthrough infection.

With age as a potential confounding factor, the researchers reanalyzed the results, but only included patients under the age of 60. Similarly to their previous findings, the researchers discovered a positive association between cross-neutralization against SARS-CoV-2 variants and the time interval between vaccination and infection breakthrough.

Source: 10.1101/2021.12.28.21268481

Image Credit: Getty

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