Heterologous COVID-19 vaccination with the ChAdOx1 nCoV-19 and BNT162b2 vaccines increases in vitro neutralizing activity and may confer cross-protection against endemic seasonal human coronaviruses (hCoV), according to results of a study published in Clinical Infectious Diseases.

In this cohort study, researchers assessed sera derived from 24 patients to determine whether prior heterologous COVID-19 vaccination confers neutralizing activity against seasonal hCoVs. Eligible patients included those aged 25 to 46 years who had received the ChAdOx1 vaccine and were subsequently boosted with the BNT612b2 vaccine. Serum antibodies were assessed 2 days prior to initial COVID-19 vaccination, and postimmunization serum antibodies were assessed 2 weeks after receipt of the BNT162b booster. Patients previously infected with COVID-19 were excluded. The researchers assessed neutralizing activity against 3 hCoVs: OC43, NL63, and 229E. They also assessed neutralizing activity against viral pseudoparticles carrying the SARS-CoV-1, SARS-CoV-2; Middle East respiratory syndrome (MERS)-CoV; and hCoVs OC43, NL63, and 229E spike proteins. Neutralization efficiencies were measured via viral RNA yields, intracellular viral nucleocapsid expression, and Huh-7 cell gene expression.

Among all included patients, the researchers found that sera obtained both prior to and after heterologous COVID-19 vaccination efficiently neutralized hCoV-OC43. Analysis of sera obtained prior to heterologous COVID-19 vaccination showed a decrease in hCoV-OC43 RNA production (half maximal inhibitory concentration [IC50], 0.09%). Although the researchers observed effective preexisting neutralizing activity against hCoV-OC43, additional increases in neutralizing activity against hCoV-OC43 were observed after heterologous COVID-19 vaccination.

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Compared with hCoV-OC43, the researchers noted preexisting neutralizing activity against hCoV-NL63 was associated with significantly increased variation and decreased efficiency. Sera obtained from patients following heterologous COVID-19 vaccination had significantly increased neutralizing activity against hCoV-NL63 compared with sera obtained prior to vaccination. There was a mean 2-fold increase in neutralizing activity against hCoV-NL63 after heterologous COVID-19 vaccination. In regard to hCoV-229E, there was a mean 4-fold increase in neutralization efficiency following heterologous COVID-19 vaccination.

Despite variations in preexisting immunity against hCoVs OC43, NL63, and 229E, increased neutralizing activity against all 3 hCoVs was observed among all patients following heterologous COVID-19 vaccination.

This study was limited by its small sample size.

In regard to heterologous COVID-19 vaccination, the researchers noted that, “strong protection against infection seems unlikely because the boosting effect of COVID-19 vaccination was usually modest and common cold viruses cause [repeat] infections despite preexisting immunity.” They concluded that “…it will be of interest to examine whether the course of seasonal [hCoV] infections is affected by COVID-19 vaccination.”


Lawrenz J, Xie Q, Zech F, et al. SARS-CoV-2 vaccination boosts neutralizing activity against seasonal human coronaviruses. Clin Infect Dis. Published online January 25, 2022. doi.10.1093/cid/ciac057