Study finds two doses of COVID-19 vaccines were insufficient to neutralize the SARS-CoV-2 Omicron variant

By Tarun Sai LomteReviewed by Danielle Ellis, B.Sc.Feb 24 2022

In a recent study posted to the medRxiv* preprint server, researchers determined the neutralization potency of sera from people vaccinated with Pfizer's Comirnaty (BNT162b2), Moderna's Spikevax (mRNA-1273), or AstraZeneca's Vaxzevria (ChAdOx1) against the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Omicron variant.

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources

Background

SARS-CoV-2, the causal agent of coronavirus disease 2019 (COVID-19) pandemic, has infected over 430 million individuals causing more than 5.9 million deaths worldwide. Globally, more than 10 billion COVID-19 vaccines have been administered so far. Vaccine-resource-rich nations have successfully immunized a vast majority of their eligible population.

At the same time, low-income countries continue to face challenges with just 14.2 vaccines inoculated per 100 people in these nations. Although SARS-CoV-2 vaccines are highly effective in eliciting immune responses, they do not nullify the odds of contracting SARS-CoV-2.

The emergence of mutant variants throughout the pandemic has exacerbated the current crisis as vaccine-breakthrough cases and reduced efficiency of vaccines against the mutant variants have been well documented. About five SARS-CoV-2 variants of concern (VOCs) are detected, namely, the Alpha, Beta, Gamma, Delta, and Omicron variants. SARS-CoV-2 Omicron is the most mutated variant among other VOCs and is responsible for the recent exponential surge of COVID-19 infections.

The study

In the current study, researchers evaluated the neutralizing potency of sera from individuals vaccinated with BNT162b2, mRNA-1273, or ChAdOx1 vaccines against the Delta and Omicron VOCs in Australia. The assessment of their potential to neutralize these VOCs is crucial because one or more vaccines are being used in around 192 countries.

The authors worked with three isolates of SARS-CoV-2 - VIC31 (as a reference strain) with the D614G mutation, Delta, and Omicron VOCs propagating them in Vero E6 cells to obtain viral stocks. Blood samples were obtained from healthy vaccinated subjects aged 25 to 70 years who received either of the three vaccines. Human blood specimens were collected at four timepoints - first on the day of vaccination (baseline; pre-first dose), second and third after two weeks (2wk-second dose), and six months (6mo-second dose) post double vaccine dose. The fourth specimen was collected exclusively from Pfizer vaccinees two weeks after the third dose (2wk-third dose).

Virus neutralization assays (VNT) were performed using Vero E6 cells. The researchers constructed in silico models of the Omicron (BA.1.1) spike protein and simulated for over 200 nanoseconds (ns).

Findings

The median age of the ChAdOx1 recipients was 57.5 years, relatively higher than 33 years for Comirnaty and 38.5 years for the Spikevax vaccinees because the AstraZeneca vaccine is used in people above 60 years due to the concerns of thrombotic thrombocytopenia syndrome (TTS) in the younger population.

Sera samples (6mo-second dose) from Comirnaty recipients showed an 8.2- and 5.5-fold reduction in neutralizing titers (NT₅₀) against VIC31 and Delta strains, respectively, when compared to 2wk-second dose specimens. After administering a third dose of BNT162b2, sera (2wk-third dose) specimens demonstrated a 25.5- and 24.7-fold increase in NT₅₀ titers against VIC31 and Delta isolates, respectively, when compared to 6mo-second dose samples.

No significant differences in NT₅₀ titers were observed for 2wk-second dose specimens from Comirnaty and Spikevax recipients. Two weeks and six months post-second vaccination, the average NT₅₀ titers were below the detection limit (LoD) for most Comirnaty samples (just four out of 15 samples had quantifiable titers), but they increased after the third dose.

Conclusions

The study findings demonstrated that two doses of any of the vaccines tested were insufficient to neutralize the Omicron variant. Notably, the vaccine-induced protection is considerably lower after six months of the second Comirnaty dose, indicating significant waning over time. Interestingly, all vaccines based on the ancestral strain of SARS-CoV-2 were ineffective in neutralizing the Omicron variant, and the NT₅₀ titers were below the LoD for all samples of BNT162b2 recipients at six months after the second dose. However, a third Comirnaty dose produced a booster effect demonstrating quantifiable NT₅₀ titers two weeks post-boosting.

Several factors limit the study findings: No 6mo-second dose samples were available for individuals vaccinated with either Spikevax or Vaxzevria vaccine. Booster dose specimens were present for only Comirnaty vaccinees. These limitations were primarily because the AstraZeneca vaccine was limited to older people, and Spikevax was introduced in August 2021 in Australia.

Based on the observations made in this study, it is imperative to note that two doses of vaccines made to imitate the Spike protein of the wildtype SARS-CoV-2 are inadequate to neutralize the highly mutant Omicron variant and that the third dose could be effective to boost the immune system.

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources