A 20-month longitudinal study to evaluate humoral and cellular immunity after COVID-19 vaccines

The effectiveness of coronavirus disease 2019 (COVID-19) vaccines is well established; however, the long-term durability of vaccine-induced immunity remains to be fully elucidated.

This study longitudinally compared humoral and cellular immune responses in two groups: G1, who received two doses of Sinovac-CoronaVac, and G2, who received two doses of AstraZeneca-Oxford, both subsequently boosted with Pfizer.

Immune responses were assessed at five time points: P1 (prior to the second dose), P2 (90-180 days after the second dose), P3 (pre-booster, six-eight months post-second dose), P4 (90-180 days post-booster), and P5 (180-270 days post-booster). Anti-Spike severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG levels were measured by enzyme-linked immunosorbent assay (ELISA), while IFNγ-producing cells in response to Spike peptides were quantified using enzyme-linked immune absorbent spot (ELISPOT). IgG subclasses were analysed in a subset of samples.

Following the first dose, Sinovac-CoronaVac induced lower anti-Spike IgG levels than AstraZeneca-Oxford, though levels equalised after the second dose. After the Pfizer booster, anti-Spike IgG levels remained elevated for up to six months in both groups. IgG1 was predominant in both groups, with occasional expression of IgG2 and IgG4. The mean frequency of IFNγ-producing cells was lower in the Sinovac-CoronaVac group before and up to six months after the second dose, compared to AstraZeneca-Oxford. However, post-Pfizer booster, both means became comparable. Between 90-180 days post-booster, the Sinovac-CoronaVac + Pfizer group exhibited a statistically significant decline in IFNγ-producing cells relative to the AstraZeneca-Oxford + Pfizer group. By P5, over half of individuals in the Sinovac-CoronaVac + Pfizer group demonstrated no detectable cellular response.

High antibody levels were maintained for up to six months following both homologous and heterologous vaccination. However, cellular immunity declined more markedly in the Sinovac-CoronaVac + Pfizer group, resulting in a higher proportion of non-responders. These findings underscore the importance of tailored booster strategies to sustain protective immunity against COVID-19.