Comparable antibody levels in heterologous and homologous mRNA COVID-19 vaccination, with superior neutralizing and IgA antibody responses in mRNA homologous boosting

Vaccine. 2024 Oct 3;42(23):126042. doi: 10.1016/j.vaccine.2024.06.010. Epub 2024 Jun 5.

Abstract

Background: Priming with two doses of AZD1222 (Oxford-AstraZeneca; ChAd) followed by a third mRNA vaccine boosting is considered in several countries, yet comparisons between heterologous and homologous booster efficacy remain unexplored.

Aim: To evaluate and contrast the immunogenicity of homologous and heterologous boosting regimens.

Method: The study examined antibody responses in 1113 subjects, comprising 895 vaccine-naïve individuals across different vaccination strategies (partial, primary series, heterologous booster, homologous booster) and 218 unvaccinated, naturally infected individuals. Assessments included neutralizing total antibodies (NTAbs), total antibodies (TAbs), anti-S-RBD IgG, and anti-S1 IgA levels.

Results: The study found mRNA vaccines to exhibit superior immunogenicity in primary series vaccination compared to ChAd, with mRNA-1273 significantly enhancing NTAbs, TAbs, anti-S-RBD IgG, and anti-S1 IgA levels (p < 0.001). Both booster types improved antibody levels beyond primary outcomes, with no significant difference in TAbs and anti-S-RBD IgG levels between regimens. However, homologous mRNA boosters significantly outperformed heterologous boosters in enhancing NTAbs and anti-S1 IgA levels, with the BNT/BNT/BNT regimen yielding particularly higher enhancements (p < 0.05).

Conclusion: The study concludes that although TAbs and anti-S-RBD IgG antibody levels are similar for both regimens, homologous mRNA boosting outperform heterologous regimen by enhancing anti-S1 IgA and neutralizing antibody levels.

Keywords: AZD1222 (Oxford-AstraZeneca, ChAd); Anti-S1 IgA; Heterologous; Homologous; Neutralizing antibody; mRNA vaccination.

MeSH terms

  • 2019-nCoV Vaccine mRNA-1273 / administration & dosage
  • 2019-nCoV Vaccine mRNA-1273 / immunology
  • Adult
  • Aged
  • Antibodies, Neutralizing* / blood
  • Antibodies, Neutralizing* / immunology
  • Antibodies, Viral* / blood
  • Antibodies, Viral* / immunology
  • COVID-19 Vaccines* / administration & dosage
  • COVID-19 Vaccines* / immunology
  • COVID-19* / immunology
  • COVID-19* / prevention & control
  • Female
  • Humans
  • Immunization, Secondary* / methods
  • Immunogenicity, Vaccine
  • Immunoglobulin A* / immunology
  • Immunoglobulin G* / blood
  • Immunoglobulin G* / immunology
  • Male
  • Middle Aged
  • SARS-CoV-2* / genetics
  • SARS-CoV-2* / immunology
  • Spike Glycoprotein, Coronavirus / genetics
  • Spike Glycoprotein, Coronavirus / immunology
  • Vaccination / methods
  • Young Adult
  • mRNA Vaccines / immunology

Substances

  • Antibodies, Neutralizing
  • Immunoglobulin A
  • Antibodies, Viral
  • COVID-19 Vaccines
  • Immunoglobulin G
  • Spike Glycoprotein, Coronavirus
  • mRNA Vaccines
  • 2019-nCoV Vaccine mRNA-1273