This prospective study provides data on the long-term humoral immunogenicity of a heterologous off-label vaccine regimen combining the adenoviral-vectored ChAdOx1 nCoV-19 from Astra-Zeneca (ChAd) with the mRNA-1273 vaccine from Moderna (m1273) in comparison with two different homologous mRNA vaccine schedules. Of the 316 COVID-19 naïve adult health care workers (HCW) included to complete a survey on vaccine-associated symptoms (VAS), 197 had received the homologous BNT162b2 mRNA vaccine from Pfizer/BioNTech (BNT/BNT), 76 the homologous m1273/m1273, and 43 the heterologous ChAd/m1273 vaccine regimen. The concentration of antibodies against SARS-CoV-2 spike protein in plasma 5–7 months after the second vaccine dose was higher in the m1273/m1273 and ChAd/m1273 than the BNT/BNT vaccine group. The frequency of systemic VAS after the first vaccine dose was 86% after ChAd compared with 35% and 39% after BNT and m1273, respectively (p < 0.0001), and after the second vaccine dose, the highest (89%) in the m1273/m1273 group (p < 0.001). Individuals with systemic VAS achieved higher levels of antibodies irrespective of vaccine regimen. In conclusion, VAS serve as a strong predictor of long-term humoral immune response, and the heterologous ChAd/m1273 vaccine regimen provides an at least equal long-term humoral immune response compared with the standard vaccine regimens used in Denmark.

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Long-Term Antibody Response against SARS-CoV-2 in Health Care Workers: Effectiveness of Homologous and Heterologous Regimens and Their Relation to Systemic Vaccine-Associated Symptoms

Heterologous vaccination regimens could contribute to broadening vaccination coverage. To date, there is little evidence on the effectiveness of a combination of adenoviral COVID-19 vaccines with a second dose of mRNA vaccines. This study aims to evaluate the antibody response to the SARS-CoV-2 spike protein 25 weeks after vaccination with mRNA-1273 after a first dose of ChAdOx1. A cross-sectional study was conducted collecting sociodemographic data, clinical characteristics, and serological data from among the general population. Antibody levels were expressed as binding antibody units (BAU) per mL (cutoff = 33.8 BAU/mL). Linear regression models were used to assess the relationship between the subjects’ characteristics and anti-SARS-CoV-2 antibody levels. A total of 229 participants were followed up after a median time of 173 days. The overall anti-SARS-CoV-2 IgG antibody titer was 729.0 BAU/mL. The multivariable analysis showed that the only factor associated with anti-SARS-CoV-2 IgG levels was the BMI (p = 0.007), with decreases within the healthy range weight and increases in under- or overweight people. Our results support the use of heterologous COVID-19 vaccination regimens, as they can guarantee a sustained immune antibody response. More studies are needed to understand the link between BMI and body composition and the immune response to COVID-19 vaccinations.

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Massimiliano Victor Leone

Papers

Immune Response of a Heterologous mRNA-1273 Second-Dose Immunization after a First Dose of ChadOx1 against SARS-CoV-2: A Cross-Sectional Study