Exploring SARS-CoV-2 Omicron variant’s neutralizing capacity of booster vaccines

In a recent study published in the medRxiv* preprint server, researchers analyzed the neutralization of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron and D614G variants before and after receiving coronavirus disease 2019 (COVID-19) booster vaccinations.

Study: SARS-CoV-2 Omicron Neutralization After Heterologous Vaccine Boosting. Image Credit: hedgehog94/ShutterstockStudy: SARS-CoV-2 Omicron Neutralization After Heterologous Vaccine Boosting. Image Credit: hedgehog94/Shutterstock

The study concluded that the heterologous and homologous booster vaccine combinations examined were associated with a boost in humoral immunity against the Omicron variant.


The SARS-CoV-2 Omicron variant (B.1.1.529) was first reported to the World Health Organization (WHO) on 24 November 2021. Omicron has more than 15 mutations in its spike (S) protein region and is associated with higher transmissibility and immune escape from COVID-19 vaccination, previous infection, and therapeutic antibodies.

Studies show that the Omicron variant is now the dominant circulating SARS-CoV-2 strain in the United States (US).

Due to the surge of SARS-CoV-2 Omicron cases and waning vaccine effectiveness, booster dose vaccination campaigns were initiated in many countries worldwide, including the US. However, detailed information about the Omicron neutralization associated with homologous and heterologous booster vaccines is not yet available.

About the study

In the current study, researchers determined the neutralization of Omicron and D614G before and 28 days after the heterologous or homologous booster vaccinations, where the booster intervals ranged from three to six and a half months.

Subset analyses were conducted using randomly selected samples forming 10 participants aged 18-55 years and 10 subjects aged 56 years or older per group for six vaccine combinations.

There were four homologous primary-booster vaccine combinations: two 100-μg doses of mRNA-1273 (Moderna) vaccine followed by boosting with either 50-μg or 100-μg dose of the same vaccine, a single 5×1010 virus particles dose of Ad26.COV2.S (Janssen) vaccine followed by a boost with the same vaccine, and two 30-μg doses of BNT162b2 (Pfizer-BioNTech) followed by a boost with the same vaccine; and two heterologous primary-booster vaccine combinations: Pfizer-BioNTech followed by Janssen vaccine and Janssen followed by the Pfizer-BioNTech vaccine.

The 50% serum neutralizing antibody (NAb) titers were determined using a lentivirus-based pseudovirus assay against the D614G reference standard obtained from all groups except the 50-μg mRNA-1273 homologous boosted individuals, and Omicron S variants from pre-boost and 29 days post-boost samples.


According to the results, NAb titers against D614G was detected in 85-100% of participants on the day of booster vaccination, with geometric mean titers (GMT) of 71-343 and 35-41 with Emergency Use Authorization (EUA) mRNA vaccine series and those primed with Janssen vaccines, respectively.

On the day of a booster dose, baseline NAb titers against Omicron were detected in 50-90% of subjects who received a EUA mRNA vaccine series and 20-25% of participants primed with the Janssen vaccine. NAb titers to Omicron were 6.0-14.0-fold lower than the D614G variant.

Most combinations of the booster vaccination increased the neutralizing GMTs to above 1000 for D614G and 250 for Omicron.  

Participants who received the homologous primary-booster Janssen vaccine combination had the lowest NAb titer with GMTs of 128 and 45 for D614G and Omicron, respectively, on the 29th day. After the booster vaccination, the GMTs for Omicron were 2.3-7.5-fold lower than D614G and were similar across all age groups.

In most combinations examined, homologous or heterologous boosters with current EUA vaccines result in post-boost titers to Omicron that provide more than 85% protection against the symptomatic SARS-CoV-2 D614G and Alpha infections.

Those who received a 50-μg and 100-μg Moderna booster dose showed similar NAb titers against Omicron, including participants aged 56 years or older.


Overall, all homologous and heterologous vaccine combinations evaluated in the study showed an increase in post-boost NAb titer against Omicron, and the lowest NAb titer was associated with the homologous primary-booster Janssen vaccination.

Further, booster vaccination reduced the differences between NAb titers for D614G and Omicron.

The study indicated possible protection against Omicron infection and disease severity conferred by booster vaccine-induced NAbs, supporting the use of COVID-19 booster vaccines as a mitigation measure against SARS-CoV-2 Omicron infection.

However, further studies demonstrating real-world effectiveness data, the kinetics of the NAb post-boost, and in-depth information about cell-mediated immunity in association with protection against severe disease are required to confirm the findings.

*Important notice

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

Journal reference:
Shanet Susan Alex

Written by

Shanet Susan Alex

Shanet Susan Alex, a medical writer, based in Kerala, India, is a Doctor of Pharmacy graduate from Kerala University of Health Sciences. Her academic background is in clinical pharmacy and research, and she is passionate about medical writing. Shanet has published papers in the International Journal of Medical Science and Current Research (IJMSCR), the International Journal of Pharmacy (IJP), and the International Journal of Medical Science and Applied Research (IJMSAR). Apart from work, she enjoys listening to music and watching movies.


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