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Heterogeneity of SARS-CoV-2 immune responses after the nationwide Omicron wave in China
Jing Wu1,2, Mingzheng Jiang1,2, Jiwei Li1,2
1Department of Respiratory, Critical Care and Sleep Medicine, School of Medicine, Xiamen University, Xiang'an Hospital of Xiamen University, Xiamen, Fujian, China.
Abstract:
It remains unclear how previous infections and vaccinations influenced and shaped heterogeneous immune responses against Omicron and its variants in diverse populations in China. After the national wave of Omicron in early 2023, we evaluated serum levels of neutralizing antibodies (nAbs) against Omicron (B.1.1.529) and its variants (BA.5, BF.7, and CH1.1) in 33 COVID-19 convalescents and 40 uninfected vaccinees, using vesicular stomatitis virus-based pseudovirus neutralizing assay. In addition, we followed 34 Delta convalescent patients to compare their immune responses against Omicron before (late 2021) and after the Omicron wave (early 2023). NAbs at the acute phase of the disease were investigated in 50 Omicron inpatients, including 24 vaccinated and 26 unvaccinated patients. Among them, nasal mucosal IgA levels were measured in 42 subjects. Compared to vaccination, breakthrough infections significantly increased the breadth and magnitude of serum nAbs and mucosal IgA levels against Omicron variants. Exposure to Omicron but not Delta elicited stronger pan-Omicron responses. In Omicron inpatients, nAbs continued to rise as vaccination doses increased. However, in both vaccinees and convalescents, a fourth dose vaccination did not elicit higher nAbs against Omicron. Furthermore, nAbs against Omicron variants lasted longer than nAbs against WT SARS-CoV-2. Breakthrough infections of Omicron variants elicited specific immune responses against Omicron compared to vaccination and Delta infection. Although repeated vaccination revealed limited impacts on serum nAbs, populations at high risk of hospitalization may still benefit from continued vaccination.IMPORTANCEThe study described the specific humoral immunity against Omicron and its variants (BA.5, BF.7, and CH1.1) in diverse populations, including Delta-positive convalescent patients, Omicron-infected patients with a previous or current confirmed Delta infection, Omicron-positive patients, and healthy controls. In addition, we followed Delta convalescents for 1 year to evaluate the effect of a booster vaccine, breakthrough infection, and reinfection. Nasal mucosal IgA levels against SARS-CoV-2 were also examined. The findings of this study demonstrated the varied responses of individuals in different states following the outbreak of Omicron, highlighting the potential advantages of ongoing immunization for groups that are more vulnerable and have a greater likelihood of being hospitalized.
Insights
Omicron breakthrough infections significantly boosted neutralizing antibodies and mucosal IgA more than vaccination. Repeated vaccination showed limited impact, but high-risk groups may benefit from continued COVID-19 immunization.
Area of Science:
- Immunology
- Virology
- Public Health
Background:
- Understanding heterogeneous immune responses to SARS-CoV-2 Omicron variants is crucial, especially in diverse populations with varied infection and vaccination histories.
- Previous infections (Delta) and vaccinations influence immunity, but their specific impact on Omicron variant responses remains unclear.
Purpose of the Study:
- To evaluate serum neutralizing antibody (nAb) and mucosal IgA levels against Omicron and its variants in different populations in China.
- To compare immune responses following breakthrough infections versus vaccination.
- To assess the long-term effects of infection and vaccination on humoral immunity.
Main Methods:
- Vesicular stomatitis virus-based pseudovirus neutralizing assay to measure nAbs against Omicron (B.1.1.529) and variants (BA.5, BF.7, CH1.1).
- Analysis of serum nAbs and nasal mucosal IgA in COVID-19 convalescents and vaccinees.
- Longitudinal follow-up of Delta convalescent patients.
Main Results:
- Breakthrough Omicron infections significantly increased the breadth and magnitude of serum nAbs and mucosal IgA compared to vaccination.
- Omicron exposure elicited stronger pan-Omicron responses than Delta exposure.
- While nAbs rose with vaccination doses in Omicron inpatients, a fourth dose did not further increase nAbs in vaccinees or convalescents.
- nAbs against Omicron variants demonstrated longer persistence than against the wild-type SARS-CoV-2.
Conclusions:
- Omicron breakthrough infections induce more robust and broader humoral immunity than vaccination alone.
- While repeated vaccination has limited impact on nAb levels, ongoing immunization may still benefit high-risk populations.
- Immune responses are variant-specific, with Omicron eliciting distinct protective effects.
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