Long-Term Immune Consequences of Initial SARS-CoV-2 A.23.1 Exposure: A Longitudinal Study of Antibody Responses and Cross-Neutralization in a Ugandan Cohort
<b>Background:</b> This study assessed the long-term dynamics of neutralizing antibodies in a Ugandan cohort primarily exposed to the A.23.1 SARS-CoV-2 variant, examining how this shaped immune breadth and potency against diverse strains following infection and prototype-based vaccinatio...
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MDPI AG
2025-01-01
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| Online Access: | https://www.mdpi.com/2076-393X/13/2/143 |
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| author | Gerald Kevin Oluka Jackson Sembera Joseph Ssebwana Katende Violet Ankunda Laban Kato Ashwini Kurshan Carl Graham Jeffrey Seow Katie J. Doores Michael H. Malim Julie M. Fox Pontiano Kaleebu Jennifer Serwanga |
| author_facet | Gerald Kevin Oluka Jackson Sembera Joseph Ssebwana Katende Violet Ankunda Laban Kato Ashwini Kurshan Carl Graham Jeffrey Seow Katie J. Doores Michael H. Malim Julie M. Fox Pontiano Kaleebu Jennifer Serwanga |
| author_sort | Gerald Kevin Oluka |
| collection | DOAJ |
| description | <b>Background:</b> This study assessed the long-term dynamics of neutralizing antibodies in a Ugandan cohort primarily exposed to the A.23.1 SARS-CoV-2 variant, examining how this shaped immune breadth and potency against diverse strains following infection and prototype-based vaccination. <b>Methods:</b> We conducted a 427-day retrospective analysis of 41 participants across multiple SARS-CoV-2 waves, assessing binding and neutralizing antibody responses using in-house ELISA and pseudotyped virus neutralization assays. We quantified immune responses to key SARS-CoV-2 variants, A.23.1, D614G, Delta, and BA.4, capturing evolving immunity across the pandemic. <b>Results:</b> Neutralizing antibody titers against A.23.1 remained significantly higher than those against D614G, Delta, and BA.4, highlighting the solid immune memory following A.23.1 infection. Consistently lower titers were observed for BA.4 across all time points, aligning with its strong immune-evasion capability. Correlations between neutralizing titers and spike-directed IgG (S-IgG) concentrations were significantly stronger for A.23.1 than for D614G, with no correlation for BA.4. ChAdOx1-S vaccination substantially elevated the neutralizing titers across all variants, most notably BA.4, highlighting the essential role of vaccination in boosting immunity, even in individuals with initially low titers. <b>Conclusions:</b> Initial exposure to the A.23.1 variant triggered potent immune responses, shaping neutralizing antibody dynamics during subsequent exposures. These findings highlight the importance of accounting for early viral exposures in vaccine development and public health planning. The distinctly lower immune response to BA.4 highlights the need for continuous antigenic monitoring and timely vaccine updates for protection against emerging variants. Vaccination remains essential for reinforcing and sustaining immunity against evolving variants. |
| format | Article |
| id | doaj-art-519c7d3ecf3a4d05bb00b541737d3366 |
| institution | OA Journals |
| issn | 2076-393X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj-art-519c7d3ecf3a4d05bb00b541737d33662025-08-20T02:03:31ZengMDPI AGVaccines2076-393X2025-01-0113214310.3390/vaccines13020143Long-Term Immune Consequences of Initial SARS-CoV-2 A.23.1 Exposure: A Longitudinal Study of Antibody Responses and Cross-Neutralization in a Ugandan CohortGerald Kevin Oluka0Jackson Sembera1Joseph Ssebwana Katende2Violet Ankunda3Laban Kato4Ashwini Kurshan5Carl Graham6Jeffrey Seow7Katie J. Doores8Michael H. Malim9Julie M. Fox10Pontiano Kaleebu11Jennifer Serwanga12Viral Pathogens Research Theme, Medical Research Council, Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine (MRC/UVRI & LSHTM) Research Unit, Entebbe 26, UgandaDepartment of Immunology, Uganda Virus Research Institute, Entebbe 26, UgandaViral Pathogens Research Theme, Medical Research Council, Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine (MRC/UVRI & LSHTM) Research Unit, Entebbe 26, UgandaViral Pathogens Research Theme, Medical Research Council, Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine (MRC/UVRI & LSHTM) Research Unit, Entebbe 26, UgandaViral Pathogens Research Theme, Medical Research Council, Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine (MRC/UVRI & LSHTM) Research Unit, Entebbe 26, UgandaDepartment of Infectious Diseases, School of Immunology & Microbial Sciences, King’s College London, London SE1 9RT, UKDepartment of Infectious Diseases, School of Immunology & Microbial Sciences, King’s College London, London SE1 9RT, UKDepartment of Infectious Diseases, School of Immunology & Microbial Sciences, King’s College London, London SE1 9RT, UKDepartment of Infectious Diseases, School of Immunology & Microbial Sciences, King’s College London, London SE1 9RT, UKDepartment of Infectious Diseases, School of Immunology & Microbial Sciences, King’s College London, London SE1 9RT, UKDepartment of Infectious Diseases, School of Immunology & Microbial Sciences, King’s College London, London SE1 9RT, UKViral Pathogens Research Theme, Medical Research Council, Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine (MRC/UVRI & LSHTM) Research Unit, Entebbe 26, UgandaViral Pathogens Research Theme, Medical Research Council, Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine (MRC/UVRI & LSHTM) Research Unit, Entebbe 26, Uganda<b>Background:</b> This study assessed the long-term dynamics of neutralizing antibodies in a Ugandan cohort primarily exposed to the A.23.1 SARS-CoV-2 variant, examining how this shaped immune breadth and potency against diverse strains following infection and prototype-based vaccination. <b>Methods:</b> We conducted a 427-day retrospective analysis of 41 participants across multiple SARS-CoV-2 waves, assessing binding and neutralizing antibody responses using in-house ELISA and pseudotyped virus neutralization assays. We quantified immune responses to key SARS-CoV-2 variants, A.23.1, D614G, Delta, and BA.4, capturing evolving immunity across the pandemic. <b>Results:</b> Neutralizing antibody titers against A.23.1 remained significantly higher than those against D614G, Delta, and BA.4, highlighting the solid immune memory following A.23.1 infection. Consistently lower titers were observed for BA.4 across all time points, aligning with its strong immune-evasion capability. Correlations between neutralizing titers and spike-directed IgG (S-IgG) concentrations were significantly stronger for A.23.1 than for D614G, with no correlation for BA.4. ChAdOx1-S vaccination substantially elevated the neutralizing titers across all variants, most notably BA.4, highlighting the essential role of vaccination in boosting immunity, even in individuals with initially low titers. <b>Conclusions:</b> Initial exposure to the A.23.1 variant triggered potent immune responses, shaping neutralizing antibody dynamics during subsequent exposures. These findings highlight the importance of accounting for early viral exposures in vaccine development and public health planning. The distinctly lower immune response to BA.4 highlights the need for continuous antigenic monitoring and timely vaccine updates for protection against emerging variants. Vaccination remains essential for reinforcing and sustaining immunity against evolving variants.https://www.mdpi.com/2076-393X/13/2/143immune imprintingSARS-CoV-2 A.23.1 variantcross-neutralizationantibody dynamicsneutralizing titersantigenic surveillance |
| spellingShingle | Gerald Kevin Oluka Jackson Sembera Joseph Ssebwana Katende Violet Ankunda Laban Kato Ashwini Kurshan Carl Graham Jeffrey Seow Katie J. Doores Michael H. Malim Julie M. Fox Pontiano Kaleebu Jennifer Serwanga Long-Term Immune Consequences of Initial SARS-CoV-2 A.23.1 Exposure: A Longitudinal Study of Antibody Responses and Cross-Neutralization in a Ugandan Cohort Vaccines immune imprinting SARS-CoV-2 A.23.1 variant cross-neutralization antibody dynamics neutralizing titers antigenic surveillance |
| title | Long-Term Immune Consequences of Initial SARS-CoV-2 A.23.1 Exposure: A Longitudinal Study of Antibody Responses and Cross-Neutralization in a Ugandan Cohort |
| title_full | Long-Term Immune Consequences of Initial SARS-CoV-2 A.23.1 Exposure: A Longitudinal Study of Antibody Responses and Cross-Neutralization in a Ugandan Cohort |
| title_fullStr | Long-Term Immune Consequences of Initial SARS-CoV-2 A.23.1 Exposure: A Longitudinal Study of Antibody Responses and Cross-Neutralization in a Ugandan Cohort |
| title_full_unstemmed | Long-Term Immune Consequences of Initial SARS-CoV-2 A.23.1 Exposure: A Longitudinal Study of Antibody Responses and Cross-Neutralization in a Ugandan Cohort |
| title_short | Long-Term Immune Consequences of Initial SARS-CoV-2 A.23.1 Exposure: A Longitudinal Study of Antibody Responses and Cross-Neutralization in a Ugandan Cohort |
| title_sort | long term immune consequences of initial sars cov 2 a 23 1 exposure a longitudinal study of antibody responses and cross neutralization in a ugandan cohort |
| topic | immune imprinting SARS-CoV-2 A.23.1 variant cross-neutralization antibody dynamics neutralizing titers antigenic surveillance |
| url | https://www.mdpi.com/2076-393X/13/2/143 |
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