Three doses of BNT162b2 able to neutralise Omicron variant

13th December 2021

Three doses of the Pfizer-BioNTech COVID-19 vaccine, BNT162b2 have been shown in a preliminary study to neutralise the Omicron variant

In a press release, Pfizer and BioNTech have announced that serum antibodies induced after three doses of their COVID-19 vaccine (BNT162b2) are able to neutralise the Omicron variant.

The company’s laboratory study involved testing human sera obtained from the blood of individuals who had received two or three 30-µg doses of the BNT162B2 using a pseudovirus neutralisation test, which used to study the effect of antibodies to neutralise the capability of viruses to enter cells and thus prevent infection. The sera were collected from subjects 3 weeks after receiving the second dose or one month after receiving the third dose of their vaccine

In the study, each sample of serum was simultaneously tested for its neutralising antibody titre against the original (or wild-type) COVID-19 spike protein as well as the Omicron spike variant. The researchers found that after a third vaccine dose, there was a significant, 25-fold increased level of neutralising antibody titres against the Omicron strain spike protein. In fact, antibody titre levels against the Omicron variant were comparable to the neutralisation against the wild-type strain observed in sera from individuals who received two doses of the companies’ COVID-19 vaccine. However, data on the persistence of these neutralising antibodies over time is uncertain and will be determined over time.

At the present time, there is still much to learn about the Omicron variant although a preliminary study from South Africa in 12 people has provided some answers. The study included 12 individuals with a mean age of 57 years (66% male), 6 of whom had been vaccinated with the remaining 6 having been both vaccinated and previously infected. The purpose of the study was to examine whether the Omicron variant still required the ACE2 receptor to gain entry to cells and if plasma from those vaccinated with BNT162b2 were able to neutralise the variant. The results showed that the ACE2 receptor was still required to gain entry to cells but also that there was a 41-fold reduction in antibody neutralisation against Omicron compared with the original wild-type. However, on the plus side, escape was much less in those who had been previously infected the COVID-19.

There is still much to learn about the Omicron variant, in particular its transmissibility and whether it results in more severe infections and hospitalisations.

However, one point reassuring point mentioned in Pfizer-BioNTech press release was how 80% of the regions of the spike protein that are recognised by cytotoxic (killer) T (CD8 +) cells are unchanged in the variant. It is possible therefore, that three doses, i.e., full vaccination and a booster, will hopefully provide an enhanced immune response and which may be sufficient to prevent the variant from causing more severe disease. 

Omicron variant nearly three-times more likely to cause re-infection

3rd December 2021

The Omicron variant of COVID-19 is potentially three times more likely to cause re-infection suggesting a substantial immune evasion

The Omicron variant (OV) of COVID-19 is potentially associated with a nearly three-fold increased risk of re-infection according to a study by South African researchers from the South African DSI-NRF Centre of Excellence in Epidemiological Modelling and Analysis, Stellenbosch University, South Africa.

Although the latest variant was only recently identified in South African where infection rates began to climb, genomic sequencing of the variant indicates that it has between 26 and 32 mutations in the spike protein, many of which are present in the receptor binding domain. However, of more concern is how many of the mutations present are associated with escape from neutralising antibodies and, as a consequence, the currently available vaccines might not be as effective.

B.1.1.529 has been deemed a variant of concern by the World Health Organization although at the present time, a good deal of information about its transmissibility, the level of disease severity and effectiveness of current vaccines remains unknown. With the appearance of an increasing number of COVID-19 variants, one key question is whether these can lead to re-infection either after natural or acquired immunity from vaccination.

For the present study, the South African team set out to determine whether the risk of re-infection had changed over time by examining rates of re-infection and whether the OV might had impacted on these rates. They used epidemiological data from the National Institute for Communicable Diseases and the line list of repeated COVID-19 tests and all positive tests are recorded in the combined data sets. Although these data are recorded as de-identified cases, the presence of repeat cases were used to calculate the time between consecutive positive tests for these individuals. Using the dates of reported infection, the researchers were able to calculate the time between successive infections for each person and the period of analysis was from the start of the pandemic in March 2020 and to the end of November 2021.

Findings

A total of 35,670 individuals with at least two suspected infections were identified, although 332 had three infections and one individual at least four. Re-infections showed a bimodal distribution, peaking near 180 and 360 days, representing the first and second waves of the pandemic.

However, for the more recent second infections (after October 2021), there were a higher number of re-infections among individuals whose primary infection had occurred during the third wave. In addition, since mid-November, re-infections were occurring in those whose primary infection had been during the first and second waves. Among those who had more than one infection, 47 experienced the third infection in November 2021 and which the authors suggested could be associated with the omicron variant.

Using regression modelling, the team determined the relative hazard ratio for re-infection to be 0.75 (95% CI 0.59 – 0.97) for wave 2 versus wave 1 and for wave 3 versus wave 1 it was 0.71. However, the hazard ratio for the period from 1 November 2021 to 27 November versus wave 1 was 2.39 (95% CI 1.88 – 3.11), i.e., the risk of re-infection was almost three times higher during November 2021.

Commenting on these findings, the authors suggested that risk of re-infection compared to a primary infection had reduced over the three waves and which was to be expected as the population gained greater immunity, even in the presence of the beta and delta variants. However, the increased rate of re-infection during November 2021 suggested that the rise was driven by the OV, although they couldn’t be certain because not all of the samples had been sequenced.

They concluded that there was evidence of a substantial increase in the risk of re-infection that has coincided with the emergence of the OV in South Africa which seemed to have a greater ability to re-infect previously infected individuals.

Citation

Pulliam JRC. Increased risk of SARS-CoV-2 reinfection associated with emergence of the Omicron variant in South Africa. MedRxiv 2021