Comparative Analysis of Nucleocapsid- and Spike-Specific Isotype Humoral Immune Responses Following Natural SARS-CoV-2 Infection and Vaccination with Sinopharm, Sinovac, and AstraZeneca
Aug 2026· Viral immunology· Vol 39, pp. 293 - 304· 0 citations· 45 references
Medicine
TL;DR
Overall, natural infection induces a coordinated humoral response biased toward the nucleocapsid antigen, supporting its utility as a marker of recent infection, whereas vaccination elicits a robust multi-subclass antibody response with platform-dependent differences in antigen recognition and subclass distribution.
Abstract
The diversity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine platforms and widespread natural exposure have created a complex landscape of humoral immunity requiring detailed characterization. Here, we compare nucleocapsid (N)- and spike (S)-specific antibody responses in sera from infected humans (IH) during the first pandemic wave (April–August 2020) and in vaccine recipients (Sinopharm, Sinovac, or AstraZeneca) using commercial ELISA kits. Among naturally IH, the IgG-positivity rate was higher for N (80.9%) than S (42.8%), with significantly elevated N-specific IgG levels compared to prepandemic controls (p-value <0.05), while IgM responses showed no significant differences. Strong positive correlations were observed between S- and N-specific antibody responses, particularly for IgG and its subclasses. Vaccinated cohorts exhibited high IgG positivity rate (83–100%) against both antigens with low IgM levels, and overall IgG and subclass responses were significantly elevated relative to pre-pandemic controls (p-value <0.05), with consistently strong inter-antigen correlations across groups. Overall, natural infection induces a coordinated humoral response biased toward the nucleocapsid antigen, supporting its utility as a marker of recent infection, whereas vaccination elicits a robust multi-subclass antibody response with platform-dependent differences in antigen recognition and subclass distribution.
Lower humoral immune responses with increasing time after heterologous mRNA booster vaccination in individuals primed with CoronaVac and may inform future booster strategies are suggested.
H. Harapan, A. P. Ayulinda, Qatrunnada Kamil et al.· Acta Tropica· 0 citations
It is shown that a Wuhan-lineage-based multi-antigen VLP vaccine can provide cross-protection against an antigenically divergent SARS-CoV-2 variant that is not fully explained by detectable serum neutralizing activity alone, suggesting the importance of integrated immune responses involving humoral, cellular, and local immune mechanisms.
Seung-Ji Kim, Howon Kim, Seung-Eun Son et al.· Vaccine· 0 citations
Data on immune responses to COVID-19 vaccination in West and Central Africa remain limited, particularly across SARS-CoV-2 variants and vaccine platforms. Using the InVITE cohort in the Democratic Republic of Congo, Guinea, Liberia, and Mali, we evaluated anti-spike (anti-S) antibody binding to nine SARS-CoV-2 variants in 96 participants equally selected from pre-vaccination assay defined seropositive and seronegative groups. Participants received mRNA, adenovirus-vectored, or inactivated virus vaccines. Anti-S binding was measured before vaccination and two months after completion of the primary series using a Meso Scale Discovery 10-plex assay. Before vaccination, antibody binding was significantly higher against pre-Omicron variants (Ancestral, Alpha, Beta, and Delta) than Omicron variants in both seronegative (fold change [FC] 3.85, 99% CI 3.45–4.17) and seropositive (FC 3.57, 99% CI 3.33–3.84) participants. Seropositive individuals showed greater binding than seronegative individuals across all variants. Two months post-vaccination, mRNA vaccines elicited higher antibody binding than adenovirus-vectored or inactivated vaccines, whereas no significant differences were observed between adenovirus-vectored and inactivated vaccines. Antibody binding remained higher against pre-Omicron than Omicron variants across all vaccine platforms and serostatus groups. These findings provide rare data on variant-specific vaccine-elicited antibody binding responses in West and Central African populations with distinct demographic, epidemiologic, and immunologic background.
Trial registration: Registration ClinicalTrials.gov: NCT05096091, Registration date: 10-26-2021, Clinical trial registry:
https://clinicaltrials.gov/study/NCT05096091?term=NCT05096091rank=1#study-overview
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E. Lusamaki, Ana M. Ortega-Villa, Daouda Camara et al.· Scientific Reports· 0 citations
The COVID-19 pandemic has highlighted the importance of understanding long-term humoral immunity after SARS-CoV-2 infection. This study evaluated the kinetics and persistence of anti-SARS-CoV-2 immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies in hospitalized patients who recovered and identified factors associated with antibody responses. A total of 96 patients hospitalized with real-time polymerase chain reaction-confirmed COVID-19 between June and September 2020 were included. Sequential serum samples were collected up to 365 days after symptom onset. Anti-SARS-CoV-2 IgM and IgG antibodies targeting spike (S) and nucleocapsid (N) proteins were evaluated on days 28, 90, 180, and 365 using chemiluminescent immunoassay (MAGLUMI). Clinical, epidemiological, and radiological data were analyzed. All convalescent patients developed detectable IgG antibodies, and 92.7% were IgG seropositive. Antibody titers and seropositivity rates declined over time; however, IgG antibodies remained more stable and persisted throughout the 12-month follow-up, whereas IgM antibodies became undetectable in most cases. Nevertheless, 12.5% of patients still had detectable IgM antibodies one year after symptom onset, whereas IgG seropositivity remained above 70%. Higher IgG titers were significantly associated with age ≥ 50 years, severe COVID-19, and SARS-CoV-2 pneumonia. Patients vaccinated before the final follow-up demonstrated a strong booster response with significantly higher IgG levels than unvaccinated individuals. In conclusion, symptomatic COVID-19 induces a durable humoral immune response that persists for at least 12 months. Hybrid immunity resulting from natural infection combined with vaccination appears to provide the strongest protection against SARS-CoV-2.
Sabrine Boufarou, N. Achour, I. Allam et al.· Microbes & Immunity· 0 citations
The COVID-19 pandemic has substantially reshaped population humoral immunity. However, whether individuals in the post-pandemic era have developed broader cross-neutralizing antibody responses against diverse coronaviruses remains unclear. To address this question, we evaluated serum neutralizing activity in 869 individuals from Wuhan, China, including 78 pre-pandemic samples collected in 2017 and 791 post-pandemic samples collected in 2025. Compared with pre-pandemic sera, post-pandemic sera exhibited enhanced neutralizing activity against multiple sarbecoviruses and the merbecovirus MjHKU4r-CoV-1, with mean viral inhibition increasing by 1.7% to 76.5% at a 1:20 serum dilution, most prominently against clade 1b sarbecoviruses. In contrast, no appreciable enhancement was observed against endemic human alphacoronaviruses or MERS-CoV. Neutralizing responses were strongly correlated across sarbecoviruses, particularly within clade 1b. Antigenic mapping showed that genetic relatedness did not reliably predict antigenic relationships, as Pangolin-GD, Pangolin-GX, and Khosta-2 were genetically more divergent yet antigenically closer to ancestral SARS-CoV-2 (D614G) than contemporary SARS-CoV-2 variants. Notably, both cohorts robustly neutralized Khosta-2, primarily through S1-directed antibodies, suggesting pre-existing cross-reactive immunity induced by endemic human coronaviruses that was further boosted by SARS-CoV-2 exposure. Collectively, these findings demonstrate that post-pandemic sera exhibit enhanced cross-neutralizing antibody responses predominantly against sarbecoviruses, potentially strengthening population immunity against related zoonotic sarbecoviruses and increasing the immunological barrier to their emergence in humans.
Shixiong Zhou, Chunhai Liu, Weiyong Liu et al.· Journal of Infection· 0 citations
The COVID-19 pandemic highlighted the need for vaccines strategies that elicit broad T cell-mediated immunity against emerging viral families. BetaCoronaviruses - including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome (MERS) and SARS-CoV-2 — pose significant pandemic risks due to their zoonotic potential and genetic diversity. In previous work, we identified conserved Spike T cell epitope regions (S-CTERs) within the ancestral Wuhan S protein sequence that demonstrated strong cross-reactive potential across diverse BetaCoronaviruses.
Here, we investigated whether bivalent vaccination (Beta + Omicron) preferentially enhances T cell responses targeting CTERs and improves cross-reactivity across Betacoronavirus subgenera. PBMC samples were collected at baseline (day 0) and post-vaccination (day 90) from a cohort of 60 adults receiving either the Pfizer or Moderna bivalent vaccine. Antigen-specific CD4+ and CD8+ T cell responses were assessed using a combined activation-induced marker (AIM) and intracellular cytokine (ICS) assay in a 25-colour-flow cytometry panel.
Overall, bivalent vaccination did not increase the response magnitude to spike or the relative fraction of S-CTER responses within total spike responses. A trend toward increased cytokine polyfunctionality was observed post-vaccination, but no significant differences were observed between pre- and post-vaccination samples across CTER pools derived from multiple BetaCoV isolates.
These findings suggest that spike-based bivalent vaccination alone cannot direct a T-cell focused response to achieve broad immunity across the BetaCoronaviruses family. Incorporation of additional protein sequences will likely be required to shift response toward the CTER approach. Understanding how bivalent vaccinations shape T cell recognition of CTER pools will be critical for advancing universal BetaCoronavirus vaccine design.
NIH
Vaccines and Immunotherapy (VAC)
Ziyin Wang, Nematullah Waseem, Naomi Peisajovich et al.· Journal of Immunology· 0 citations
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