BACKGROUND AND PURPOSE:

• In March 2021, Germany temporarily suspended administration of the adenoviral vector-based AstraZeneca COVID-19 vaccine due to incidence of thromboses
  • In response, revised recommendations suggested that individuals <60 years old that received a first dose of AstraZeneca should receive a second dose of a Pfizer or Moderna mRNA vaccine
• Schmidt et al. (Nature Medicine, 2021) assessed the immunogenicity and reactogenicity of a heterologous vector/mRNA prime–booster regimen in comparison to the standard homologous regimens

METHODS:

• Observational study
• Participants
  • Healthy adults enrolled before their second dose of vaccine
  • At enrollment no participants had a known history of SARS-CoV-2 infection
• Exposures
  • Hom vector: homologous vector/vector vaccine regimen
  • Hom mRNA: homologous mRNA/mRNA vaccine regimen
  • Het: heterologous vector/mRNA vaccine regimen
• Study design
  • Spike-specific CD4 and CD8 T cells were identified using flow cytometry by induction of CD69 and the cytokines interferon (IFN)-γ, tumor necrosis factor (TNF)-α and interleukin (IL)-2
  • Adverse events were recorded by questionnaire

RESULTS:

• Hom vector: 55 individuals | Hom mRNA: 62 individuals | Het: 96 individuals
  • The time between doses was greater for regimens with vector vaccines, as per guidelines
    • Hom vector: 10.8 ± 1.4 weeks
    • Hom mRNA: 4.3 ± 1.1 weeks
    • Het: 11.2 ± 1.3 weeks
  • Individuals in the homologous vector group were slightly older than the other two groups
  • Lymphocyte and leukocyte counts did not differ between the groups
• IgG levels were slightly lower with homologous vector vaccination, compared to the other groups (P<0.0001)
  • Hom vector: 404 (IQR 510) BAU ml^–1
  • Hom mRNA: 4,932 (IQR 4,239) BAU ml^–1
  • Het: 3,630 (IQR 3721) BAU ml^–1
• Additionally, CD4 T cell levels following homologous vector vaccination were significantly lower than the other groups (each P=0.0001)
  • Hom vector: median 0.04% (IQR 0.04%)
  • Hom mRNA: median 0.16% (IQR 0.19%)
  • Het: 0.17% (IQR 0.13%)
• The heterologous vaccine regimen induced the highest percentages of spike-specific IFN-γ-producing CD8 T cells (P<0.0001)
  • Hom vector: 0.04% (IQR 0.08%)
  • Hom mRNA: 0.06% (IQR 0.19%)
  • Het: 0.28% (IQR 0.54%)
• Spike-specific T cells were predominantly polyfunctional with largely overlapping cytokine-producing phenotypes in all three regimens
• Side effects
  • First dose
    • Greater number of systemic adverse events were reported for vector vaccine as first dose
  • Second dose
    • Homologous vector regimen was associated with fewer systemic side effects after the second dose vs other groups

CONCLUSION:

• A heterologous vaccine regimen of AstraZeneca followed by an mRNA vaccine induced strong humoral and cellular immune responses
• This heterologous regimen was well tolerated, with side effect profiles comparable to those individuals who received two mRNA doses
• The authors conclude

Although vaccine development focuses on antibodies due to their ability to confer sterilizing immunity, T cells are important in mediating protection from severe disease and may be less affected by virus variants.

The T cell data from this and similar studies could influence the development of future vaccine strategies, including how to improve vaccine-induced T cell immunity and protection from severe disease among vulnerable groups of immunocompromised patients

Learn More – Primary Sources:

Immunogenicity and reactogenicity of heterologous ChAdOx1 nCoV-19/mRNA vaccination

Related ObG Topics:

mRNA-Based COVID-19 Vaccines Induce Robust, Persistent Immune Responses in Humans

Safety and Efficacy of AstraZeneca Oxford’s COVID-19 Vaccine

AstraZeneca and Pfizer Side Effects and Efficacy: Real World Data from the UK

Potential Pathology Behind AstraZeneca COVID-19 Vaccination and Blood Clots