Adaptive immune responses in vaccinated patients with symptomatic SARS-CoV-2 Alpha infection

Abstract

Benchmarks for protective immunity from infection or severe disease after SARS-CoV-2 vaccination are still being defined. Here we characterized virus neutralizing and ELISA antibody levels, cellular immune responses, and viral variants in 4 separate groups: Healthy control participants weeks (early) or months (late) following vaccination in comparison to symptomatic SARS-CoV-2 infections after partial or full mRNA vaccination. During the study time, most symptomatic breakthrough infections were caused by the SARS-CoV-2 Alpha variant. Neutralizing antibody levels in the healthy controls were sustained over time against the vaccine parent virus, but decreased against the Alpha variant, whereas IgG titers and T cell responses against the parent virus and Alpha variant declined over time in healthy controls. Both partially and fully vaccinated patients with symptomatic infections had lower virus neutralizing antibody levels against parent virus than the healthy controls, similar IgG antibody titers and similar virus-specific T cell responses measured by IFN-g. Compared to healthy controls, neutralization activity against the Alpha variant was lower in the partially vaccinated infected patients and tended toward lower in the fully vaccinated infected patients. In this cohort of breakthrough infections, parent virus neutralization was the superior predictor of breakthrough infections with the Alpha variant of SARS-CoV-2. Summary: Despite similar antibody titers and T-cell responses to vaccinated noninfected healthy controls, neutralizing capacity was reduced in those with breakthrough infection.

SARS-CoV-2–specific immune responses in boosted vaccine recipients with breakthrough infections during the Omicron variant surge

“…However, taken together our data suggest that breakthrough infection can occur despite potent adaptive immune responses to the vaccine strain spike protein, even in young healthy boosted VRs. This is in contrast to studies that found lower neutralizing antibody and T cell responses in breakthrough VRs who were infected with the Alpha variant (20)(21)(22) and confirms a study showing high titers of spike-binding antibodies in patients with Omicron breakthrough infections (28). While only 4.4% of the participants in that study had received 3 vaccine doses, all the VRs in our study had received a booster shot.…”

“…Breakthrough infections with the Alpha variant in fully vaccinated individuals have been associated with lower titers of neutralizing antibodies (20)(21)(22) and less robust T cell responses (23). However, given that the Omicron variant has more mutations and evades neutralizing antibody responses better than prior VOCs, the mechanisms of Omicron variant breakthrough infections are likely different.…”

Association of Frailty, Age, and Biological Sex With Severe Acute Respiratory Syndrome Coronavirus 2 Messenger RNA Vaccine–Induced Immunity in Older Adults

“…For comparison between the vaccine virus and VOCs, data were expressed as the percentage of ACE2 inhibition. Live-virus microneutralization assays were performed as described elsewhere, using 2-fold dilutions of plasma incubated with infectious virus and then VeroE6-TMPRSS2 cells to measure cytopathic effect [ 25 ]. Results were expressed as the log 10 -transformed neutralizing antibody (nAb) area under the curve.…”

Recapping the Features of SARS-CoV-2 and Its Main Variants: Status and Future Paths

“…For instance, among mRNA-based vaccines, mRNA-1273 appears to display greater efficacy than BNT162b2 [ 74 ]. On the other hand, it is also important to consider the immune response generated by the individual, as there is some evidence suggesting that subjects partially or fully vaccinated with lower virus-neutralizing antibody levels were more likely to be infected by the Alpha variant [ 75 ]. The detection of IgA and IgG in the nasopharyngeal fluid appears to be directly correlated with an improved response against the Alpha variant, supporting the relevance of the humoral response to control this infection [ 76 ].…”