Jul 2026· Indian Journal of Medical Microbiology· Vol 63, pp.
101207
· 0 citations· 24 references
Medicine
TL;DR
It is observed that individuals with hybrid immunity, defined as immunity derived from both the natural infection and vaccination, exhibit significantly higher levels of neutralizing antibodies than individuals who had been solely vaccinated with COVISHIELD.
Abstract
Purpose
The COVID-19 pandemic has witnessed the rapid evolution of the SARS-CoV-2 virus, resulting in the emergence of multiple variants with mutations in critical regions of the spike protein, notably in the receptor binding domain. These mutations can lead to immune evasion and breakthrough (BT) infections, even in the vaccinated individuals. While previous studies have documented various mutations, there is a limited understanding of these mutations in different epitopes and their influence on the vaccine elicited immune response.
Methods
Neutralizing antibodies were detected using Plaque reduction neutralization test and peptide enzyme linked immunosorbent assay was standardized to identify possible epitopes contributing to immune escape. We used GraphPad Prism 9.5.0 (525) for analysis. Results were significant at p < 0.05.
Results
In this study, we observed that individuals with hybrid immunity, defined as immunity derived from both the natural infection and vaccination, exhibit significantly higher levels of neutralizing antibodies than individuals who had been solely vaccinated with COVISHIELD. Consequently, we highlight the substantial differences in the reactivity of neutralizing antibodies against the Wuhan, Delta, and Omicron variants. Our findings indicate that individuals who have recovered from COVID-19 and /or who experienced BT infections, showed stronger reactivity toward the conserved peptides than individuals vaccinated with no prior exposure.
Conclusions
COVISHIELD induced antibodies effectively neutralized original Wuhan strain but showed reduced neutralization against Delta and Omicron due to mutations in specific epitopes within their spike proteins. Mutations in variant specific epitopes can lead to evasion of the virus, emphasizing the importance of targeting linear region epitopes as critical binding sites.
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
Depletion experiments revealed that booster-induced immunity was predominantly mediated by cross-reactive antibodies, with the highest levels after breakthrough infections and the lowest after a primary WT infection, providing functional insights into the antibody specificities associated with imprinting effects following variant-adapted booster vaccination.
Iris Medits-Weiss, Dominik Moll, D. Springer et al.· Scientific Reports· 0 citations
Investigating the evolutionary dynamics of the SARS-CoV-2 Delta variant in hamsters immunized with varying doses of a full-length spike protein vaccine indicates that heterogeneous vaccine-induced immune pressure can shape intra-host SARS-CoV-2 evolution in a dose-dependent and host-specific manner and highlights the potential role of partial immunity and increased iSNVs in the upper respiratory tract in driving the emergence of putative immune-evasive viral variants.
K. Shim, J. Choi, Eun-Ha Hwang et al.· Journal of General Virology· 0 citations
The half-life (HL) of specific antibodies produced by the human body against various viruses varies from about 4 months to 11,000 years. Due to their short half-lives, multiple-dose vaccinations and annual revaccination are usually required for most viruses, which cause a large economic burden, especially in developing countries with limited storage of vaccines. Protein assemblies with a high degree of repetitiveness and organization are known to induce strong and long-lasting immune responses. However, the detailed quantitative law is still unknown. Through epitope analysis of representative viruses, we found that the longevity of immunological memory may be correlated with the number of epitopes with similar sequences (EWSS). Accordingly, a vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with 4.5-times higher antibody titers and over 100 months of HL was developed in a rabbit model. The decay pattern of antibodies against each epitope or the entire SARS-CoV-2 spike protein was roughly correlated with the number of EWSS in immunization treatments, that is, for every additional EWSS, the HL of the antibody would be doubled. This study also discusses improvement measures for vaccines against other viruses.
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 emergence of the SARS-CoV-2 pandemic led to the spread of highly transmissible variants, such as the Delta variant, which originated in India, underscoring the urgent need to develop new antivirals, therapeutics, and vaccines. In our previous study, we showed that Membrane-Envelope Virus-like Particles exhibit antigenicity and neutralization activity. Hence, our present study was conducted to evaluate whether the M protein alone can form VLPs that elicit an immune response. Using computational methods, we identified key interacting residues in M-protein that contribute to VLP formation and interact with other structural proteins, including Spike (S), Nucleocapsid (N), and Envelope (E). The SARS-CoV-2-M protein was expressed in Sf-21 insect cells, and the resulting VLPs were purified, analyzed for shape and size, and characterized using DLS, FESEM, and TEM. The purified VLPs were injected into BALB/c mice to evaluate their immune response compared with uninfected controls. The biophysical analysis confirms that the particles are round and have a size of ~ 180–200 nm. The serum levels of IgG, IgM, and IgA were found to be higher in immunized mice than in uninfected mice. Further qRT-PCR analysis demonstrated the levels of IFN-γ, IL-2, and IL-12, indicating a TH1-biased immune response against the M protein. Our study demonstrates that the highly conserved M protein can self-assemble into VLPs and elicit humoral and cellular immune response. Furthermore, our study indicates that while M-protein VLPs elicit significant antibodies and cytokine responses, they do not induce detectable neutralizing activity when given alone.
Akash Kumar, K. K. Inampudi, Vikas Kumar et al.· Virology Journal· 0 citations
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