Prior SARS-CoV-2 Infection Enhances Initial mRNA Vaccine Response with a Lower Impact on Long-Term Immunity.

Area of Science:

• Immunology
• Vaccinology
• Virology

Background:

• mRNA vaccines (Pfizer BNT162b2) reduced SARS-CoV-2 morbidity/mortality, necessitating boosters due to variants.
• Diverse immune memory arises from infection and vaccination, but long-term adaptive responses to repeated antigen exposure are unclear.

Purpose of the Study:

• To examine adaptive immune response trajectories after three mRNA vaccine doses.
• To compare responses in SARS-CoV-2-naive versus preimmune individuals.
• To assess the impact of pre-existing immunity on long-term vaccine-induced memory.

Main Methods:

• Assessed IgG, B cell, and T cell Spike-specific responses in blood samples.
• Collected samples at six time points up to 6 months post-third immunization.
• Studied individuals who received three monovalent Pfizer BNT162b2 doses without breakthrough infection.

Main Results:

• Repeated Spike antigen exposures improved IgG responses more than T cell frequency and longevity.
• Natural infection enhanced neutralizing antibodies and CD4+ T cell subsets post-initial vaccination but offered limited long-term benefit.
• After three doses, both naive and preimmune groups exhibited comparable immune memory quality and quantity.

Conclusions:

• mRNA vaccine-induced immunological memory is durable.
• Preimmunity has a limited impact on the quality and quantity of immune memory after a three-dose regimen.
• Understanding these responses is crucial for long-term COVID-19 protection strategies.