AstraZeneca First Dose and mRNA Second Dose: How Does the ‘Mix & Match’ Immune Response Stack Up?
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
Healthy adults enrolled before their second dose of vaccine
At enrollment no participants had a known history of SARS-CoV-2 infection
Hom vector: homologous vector/vector vaccine regimen
Hom mRNA: homologous mRNA/mRNA vaccine regimen
Het: heterologous vector/mRNA vaccine regimen
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
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
Greater number of systemic adverse events were reported for vector vaccine as first dose
Homologous vector regimen was associated with fewer systemic side effects after the second dose vs other groups
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
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