Elicitation of neutralizing antibodies and IgG4 subclass switching following booster vaccination with ancestral COVID-19 mRNA vaccines does not reduce breakthrough infections
Vaccination with COVID-19 mRNA vaccines generates robust antibody responses, but the impact of prior infection on the quality of these responses, particularly immunoglobulin G (IgG) subclass profiles remain unclear. A longitudinal study was conducted to compare humoral immune responses in SARS-CoV-2...
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| Format: | Article |
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Taylor & Francis Group
2025-12-01
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| Series: | Human Vaccines & Immunotherapeutics |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/21645515.2025.2547517 |
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| author | Engin Berber Erin E. Jarrett Hannah B. Hanley Naoko Uno Ted M. Ross |
| author_facet | Engin Berber Erin E. Jarrett Hannah B. Hanley Naoko Uno Ted M. Ross |
| author_sort | Engin Berber |
| collection | DOAJ |
| description | Vaccination with COVID-19 mRNA vaccines generates robust antibody responses, but the impact of prior infection on the quality of these responses, particularly immunoglobulin G (IgG) subclass profiles remain unclear. A longitudinal study was conducted to compare humoral immune responses in SARS-CoV-2 infection-naïve and pre-immune (previously infected) individuals following a two-dose mRNA vaccine primary series and a booster dose. Anti-spike receptor-binding domain (RBD) IgG levels, neutralizing antibody titers against the vaccine-matched (Wuhan-Hu-1) virus and the Omicron BA.1 variant, and IgG1–IgG4 subclass distributions over time were measured. After two doses, pre-immune participants had higher anti-RBD IgG (2-fold, p < .001) and neutralization titers than naïve participants (GMT±SD; 6407 ± 4 vs 5706 ± 3.5). Notably, 89.7% of pre-immune versus 28.1% of naïve sera neutralized Omicron BA.1 (p < .0001). However, a third (booster) raised antibody levels in naïve participants to a statistically similar titer to pre-immune participants (p > .05). The booster vaccination also markedly enhanced the titers of cross-neutralizing antibodies against Omicron BA.1 in both vaccine groups. This increased the proportion of responders from 31.8% to 95.5% in naïve participants. Booster vaccinations induced significant IgG4 titers in naïve (p < .0001), but not in pre-immune participants (p > .05) compared to primary series of vaccination levels. Both vaccinated naïve participants and pre-immune vaccinated participants had a breakthrough infection within one year following the booster vaccination (36.4% vs 25%, p > .05 respectively). We report that the presence of IgG4 antibodies, specifically in naïve individuals, did not alter in vitro virus neutralizing response against ancestral WH-1 and Omicron BA.1 variant, with comparable breakthrough infection rates. |
| format | Article |
| id | doaj-art-c75e25b5a6fd471b8a37d72554ae4a3e |
| institution | Kabale University |
| issn | 2164-5515 2164-554X |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
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| series | Human Vaccines & Immunotherapeutics |
| spelling | doaj-art-c75e25b5a6fd471b8a37d72554ae4a3e2025-08-20T04:01:01ZengTaylor & Francis GroupHuman Vaccines & Immunotherapeutics2164-55152164-554X2025-12-0121110.1080/21645515.2025.2547517Elicitation of neutralizing antibodies and IgG4 subclass switching following booster vaccination with ancestral COVID-19 mRNA vaccines does not reduce breakthrough infectionsEngin Berber0Erin E. Jarrett1Hannah B. Hanley2Naoko Uno3Ted M. Ross4Lerner Research Institute, Department of Infection Biology, Cleveland Clinic, Cleveland, OH, USACenter for Vaccines and Immunology, University of Georgia, Athens, GA, USACenter for Vaccines and Immunology, University of Georgia, Athens, GA, USALerner Research Institute, Department of Infection Biology, Cleveland Clinic, Cleveland, OH, USALerner Research Institute, Department of Infection Biology, Cleveland Clinic, Cleveland, OH, USAVaccination with COVID-19 mRNA vaccines generates robust antibody responses, but the impact of prior infection on the quality of these responses, particularly immunoglobulin G (IgG) subclass profiles remain unclear. A longitudinal study was conducted to compare humoral immune responses in SARS-CoV-2 infection-naïve and pre-immune (previously infected) individuals following a two-dose mRNA vaccine primary series and a booster dose. Anti-spike receptor-binding domain (RBD) IgG levels, neutralizing antibody titers against the vaccine-matched (Wuhan-Hu-1) virus and the Omicron BA.1 variant, and IgG1–IgG4 subclass distributions over time were measured. After two doses, pre-immune participants had higher anti-RBD IgG (2-fold, p < .001) and neutralization titers than naïve participants (GMT±SD; 6407 ± 4 vs 5706 ± 3.5). Notably, 89.7% of pre-immune versus 28.1% of naïve sera neutralized Omicron BA.1 (p < .0001). However, a third (booster) raised antibody levels in naïve participants to a statistically similar titer to pre-immune participants (p > .05). The booster vaccination also markedly enhanced the titers of cross-neutralizing antibodies against Omicron BA.1 in both vaccine groups. This increased the proportion of responders from 31.8% to 95.5% in naïve participants. Booster vaccinations induced significant IgG4 titers in naïve (p < .0001), but not in pre-immune participants (p > .05) compared to primary series of vaccination levels. Both vaccinated naïve participants and pre-immune vaccinated participants had a breakthrough infection within one year following the booster vaccination (36.4% vs 25%, p > .05 respectively). We report that the presence of IgG4 antibodies, specifically in naïve individuals, did not alter in vitro virus neutralizing response against ancestral WH-1 and Omicron BA.1 variant, with comparable breakthrough infection rates.https://www.tandfonline.com/doi/10.1080/21645515.2025.2547517mRNA vaccineCOVID-19SARS-CoV-2virus neutralizationIgG subclass switchingpre-immune |
| spellingShingle | Engin Berber Erin E. Jarrett Hannah B. Hanley Naoko Uno Ted M. Ross Elicitation of neutralizing antibodies and IgG4 subclass switching following booster vaccination with ancestral COVID-19 mRNA vaccines does not reduce breakthrough infections Human Vaccines & Immunotherapeutics mRNA vaccine COVID-19 SARS-CoV-2 virus neutralization IgG subclass switching pre-immune |
| title | Elicitation of neutralizing antibodies and IgG4 subclass switching following booster vaccination with ancestral COVID-19 mRNA vaccines does not reduce breakthrough infections |
| title_full | Elicitation of neutralizing antibodies and IgG4 subclass switching following booster vaccination with ancestral COVID-19 mRNA vaccines does not reduce breakthrough infections |
| title_fullStr | Elicitation of neutralizing antibodies and IgG4 subclass switching following booster vaccination with ancestral COVID-19 mRNA vaccines does not reduce breakthrough infections |
| title_full_unstemmed | Elicitation of neutralizing antibodies and IgG4 subclass switching following booster vaccination with ancestral COVID-19 mRNA vaccines does not reduce breakthrough infections |
| title_short | Elicitation of neutralizing antibodies and IgG4 subclass switching following booster vaccination with ancestral COVID-19 mRNA vaccines does not reduce breakthrough infections |
| title_sort | elicitation of neutralizing antibodies and igg4 subclass switching following booster vaccination with ancestral covid 19 mrna vaccines does not reduce breakthrough infections |
| topic | mRNA vaccine COVID-19 SARS-CoV-2 virus neutralization IgG subclass switching pre-immune |
| url | https://www.tandfonline.com/doi/10.1080/21645515.2025.2547517 |
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