Third dose of SARS-CoV-2 vaccine increases protection against omicron variant


Currently, the new variant Omicron or B.1.1.529 of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global cause of concern due to its ability to evade immunity and vaccine protection and to cause coronavirus disease 2019 (COVID -19).

A new study examines variation in vaccine efficacy against viral variants using estimated reductions in neutralizing antibody levels from published studies. The researchers also studied the vaccine’s effectiveness against the omicron variant.

Study: Estimates of reduced vaccine efficacy against hospitalization, infection, transmission and symptomatic illness of a new variant of SARS-CoV-2, Omicron (B.1.1.529), using titers neutralizing antibodies. Image Credit: viewimage / Shutterstock

A pre-printed version of the study, which is yet to be peer reviewed, is available on the website medRxiv* server.


The Omicron variant was reported in November 2021. SARS-CoV-2 evolves in populations highly immune to infection or vaccination with the possibility of the emergence of new variants that may escape the immune system. Determining the effectiveness of the vaccine is essential to assess the extent of immune evasion.

Vaccine effectiveness refers to the effectiveness of vaccines in the real world. Neutralizing antibody levels are a surrogate for protection against SARS-CoV-2. In addition, they can be measured quickly and give quick results. In addition, variations in neutralizing antibody levels between vaccines are strongly correlated with protection against symptomatic disease, infection, and transmission.

Traditional studies of vaccine effectiveness can be expensive. They can only be performed in the event of significant transmission of a new variant in a partially vaccinated population. Due to these limitations, there may be delays in implementing interventions until these studies can be completed. This can lead to the rapid growth of a new variant and stress on health systems.

Estimation of vaccine efficacy

The authors collected data from a recent review on the levels of neutralizing antibodies for four variants of SARS-CoV-2, namely Alpha, Beta, Gamma and Delta, and for each vaccine. Neutralizing antibody levels were normalized by convalescent sera. The estimate of the level of neutralizing antibody for one variant was divided by the level of neutralizing antibody for wild-type SARS-CoV-2 to represent the reduction as expressed by the difference factor. Wild-type SARS-CoV-2 is the original virus from Wuhan – Wuhan-Hu-1, US-WA1 / 2020, B, B.1.

The authors also calculated the mean differences between the variants and a ratio of relative neutralizing antibody titers specific to the vaccine variant (NATR).

The authors also collected data from the literature on the efficacy of the COVID-19 vaccine and the endpoint. The data were classified by type of variant (Alpha, Beta, Gamma, Delta) and by endpoint (hospitalization, symptomatic disease and documented infection). Statistical models were used to estimate the relationships between vaccine efficacy and neutralizing antibody titers per vaccine and variant.

Declining vaccine efficacy

There was considerable variation in the levels of variant-specific neutralizing antibodies between studies. However, within-study comparisons between variants were consistent.

There was not enough data to estimate the efficacy of the omicron vaccine based solely on within-vaccine comparisons between variants. The variation in vaccine efficacy with NATR between variants and vaccines showed strong relationships over a range of 30 to 110 times for all three endpoints.

There is a 40-fold reduction in the levels of neutralizing antibodies against Omicron. Omicron has increased the risk of hospitalization four to five-fold and the risk of symptomatic illness seven-to-ten for people vaccinated with mRNA vaccines. The relative effects were similar for individuals recently vaccinated or with decreased antibody titers.

The vaccine’s efficacy was 96.3% against Delta for recipients recently vaccinated with Pfizer, but 84.9% against Omicron. The decreasing vaccine efficacy was 88.8% for Delta, but 63.1% for Omicron.

The third dose of vaccine restored neutralizing antibody levels and protection. He increased the effectiveness of the vaccine to 91.7% for Omicron. However, it was similar to weakened immunity to Delta.

The relative trends were similar for Moderna vaccine recipients. The efficacy of the vaccine was somewhat higher than the Pfizer vaccine for recently vaccinated and decreased, although the third dose was less effective.


Neutralizing antibody levels are a proxy for vaccine effectiveness and may not reflect the full extent of immune evasion by the newer variants. The extent of Omicron’s immune evasion is high compared to previous variants. Because vaccine efficacy estimates for the next most evasive variant, Beta, were uncertain, it was difficult to estimate vaccine-specific models to estimate vaccine efficacy for Omicron. The 40-fold reduction estimated for Omicron required extrapolation well outside the available data. This makes it difficult to calculate reliable estimates of vaccine efficacy for Omicron for vaccinees with weakened immunity.


The effectiveness of the vaccine against serious illness is significantly reduced in debilitated people. In addition, protection against infections, symptomatic illnesses and transmission is almost eliminated. However, the third doses significantly elevate immune levels but only restore protection to levels equivalent to weakened protection against Delta. Omicron is likely to cause generalized infection and significant hospitalizations unless a generalized boost in immunity occurs.

*Important Notice

medRxiv publishes preliminary scientific reports which are not peer reviewed and, therefore, should not be considered conclusive, guide clinical practice / health-related behavior, or treated as established information.

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