Delayed Cellular Immunity in SARS-CoV-2 Antibody-Non-Responders to COVID-19 Vaccination: Rethinking Post-Vaccine...

Area of Science:

• Immunology
• Vaccinology
• Infectious Diseases

Background:

• Standard assessment of SARS-CoV-2 vaccination immunity relies on IgG antibody levels.
• Limited understanding exists regarding the timeline of vaccine-induced cellular immunity, particularly in individuals lacking detectable IgG post-vaccination.

Purpose of the Study:

• To investigate the development and timing of T-cell immunity following SARS-CoV-2 vaccination.
• Focus on individuals who did not develop detectable IgG antibodies after COVID-19 vaccination.

Main Methods:

• Cross-sectional analysis of COVID-19-naive individuals post-full SARS-CoV-2 vaccination.
• Evaluation of T-cell response using IGRA methodology (T-SPOT® COVID).
• Comparison of T-cell response rates and levels between seropositive and seronegative groups, with temporal cutoff analysis.

Main Results:

• In seronegative individuals, IgG levels negatively correlated with time post-vaccination, while T-cell response showed a weak positive time trend.
• A critical time point was identified at 80 days post-vaccination, after which T-cell response rates and levels significantly increased.
• Individuals tested after 80 days demonstrated higher median T-cell response levels and a greater positive T-cell response rate (67% vs. 38%).

Conclusions:

• Cellular immunity against SARS-CoV-2 may manifest later than antibody responses in non-responders.
• The 80-day mark post-vaccination is a critical time point for detecting robust T-cell immunity.
• Results advocate for incorporating cellular assays into post-vaccination monitoring and revising vaccine response evaluation criteria.