Obesity Is Associated with an Impaired Baseline Repertoire of Anti-Influenza Virus Antibodies
ABSTRACT Obesity is a risk factor for severe disease and mortality for both influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. While previous studies show that individuals with obesity generate antibody responses following influenza vaccination, infection rates wit...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2023-06-01
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| Series: | Microbiology Spectrum |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.00010-23 |
| _version_ | 1797803462428196864 |
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| author | Marwa Abd Alhadi Lilach M. Friedman Erik A. Karlsson Liel Cohen-Lavi Anat Burkovitz Stacey Schultz-Cherry Terry L. Noah Samuel S. Weir Lester M. Shulman Melinda A. Beck Tomer Hertz |
| author_facet | Marwa Abd Alhadi Lilach M. Friedman Erik A. Karlsson Liel Cohen-Lavi Anat Burkovitz Stacey Schultz-Cherry Terry L. Noah Samuel S. Weir Lester M. Shulman Melinda A. Beck Tomer Hertz |
| author_sort | Marwa Abd Alhadi |
| collection | DOAJ |
| description | ABSTRACT Obesity is a risk factor for severe disease and mortality for both influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. While previous studies show that individuals with obesity generate antibody responses following influenza vaccination, infection rates within the obese group were twice as high as those in the healthy-weight group. The repertoire of antibodies raised against influenza viruses following previous vaccinations and/or natural exposures is referred to here as baseline immune history (BIH). To investigate the hypothesis that obesity impacts immune memory to infections and vaccines, we profiled the BIH of obese and healthy-weight adults vaccinated with the 2010-2011 seasonal influenza vaccine in response to conformational and linear antigens. Despite the extensive heterogeneity of the BIH profiles in both groups, there were striking differences between obese and healthy subjects, especially with regard to A/H1N1 strains and the 2009 pandemic virus (Cal09). Individuals with obesity had lower IgG and IgA magnitude and breadth for a panel of A/H1N1 whole viruses and hemagglutinin proteins from 1933 to 2009 but increased IgG magnitude and breadth for linear peptides from the Cal09 H1 and N1 proteins. Age was also associated with A/H1N1 BIH, with young individuals with obesity being more likely to have reduced A/H1N1 BIH. We found that individuals with low IgG BIH had significantly lower neutralizing antibody titers than individuals with high IgG BIH. Taken together, our findings suggest that increased susceptibility of obese participants to influenza infection may be mediated in part by obesity-associated differences in the memory B-cell repertoire, which cannot be ameliorated by current seasonal vaccination regimens. Overall, these data have vital implications for the next generation of influenza virus and SARS-CoV-2 vaccines. IMPORTANCE Obesity is associated with increased morbidity and mortality from influenza and SARS-CoV-2 infection. While vaccination is the most effective strategy for preventing influenza virus infection, our previous studies showed that influenza vaccines fail to provide optimal protection in obese individuals despite reaching canonical correlates of protection. Here, we show that obesity may impair immune history in humans and cannot be overcome by seasonal vaccination, especially in younger individuals with decreased lifetime exposure to infections and seasonal vaccines. Low baseline immune history is associated with decreased protective antibody responses. Obesity potentially handicaps overall responses to vaccination, biasing it toward responses to linear epitopes, which may reduce protective capacity. Taken together, our data suggest that young obese individuals are at an increased risk of reduced protection by vaccination, likely due to altered immune history biased toward nonprotective antibody responses. Given the worldwide obesity epidemic coupled with seasonal respiratory virus infections and the inevitable next pandemic, it is imperative that we understand and improve vaccine efficacy in this high-risk population. The design, development, and usage of vaccines for and in obese individuals may need critical evaluation, and immune history should be considered an alternate correlate of protection in future vaccine clinical trials. |
| first_indexed | 2024-03-13T05:21:16Z |
| format | Article |
| id | doaj.art-5f3c29fb1aab4827b4cefeb07cc536d6 |
| institution | Directory Open Access Journal |
| issn | 2165-0497 |
| language | English |
| last_indexed | 2024-03-13T05:21:16Z |
| publishDate | 2023-06-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj.art-5f3c29fb1aab4827b4cefeb07cc536d62023-06-15T13:18:31ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972023-06-0111310.1128/spectrum.00010-23Obesity Is Associated with an Impaired Baseline Repertoire of Anti-Influenza Virus AntibodiesMarwa Abd Alhadi0Lilach M. Friedman1Erik A. Karlsson2Liel Cohen-Lavi3Anat Burkovitz4Stacey Schultz-Cherry5Terry L. Noah6Samuel S. Weir7Lester M. Shulman8Melinda A. Beck9Tomer Hertz10Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, IsraelDepartment of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, IsraelVirology Unit, Institute Pasteur du Cambodge, Phnom Penh, CambodiaNational Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva, IsraelDepartment of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, IsraelDepartment of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, Tennessee, USADepartment of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USADepartment of Family Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USADepartment of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, IsraelDepartment of Nutrition, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, USADepartment of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, IsraelABSTRACT Obesity is a risk factor for severe disease and mortality for both influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. While previous studies show that individuals with obesity generate antibody responses following influenza vaccination, infection rates within the obese group were twice as high as those in the healthy-weight group. The repertoire of antibodies raised against influenza viruses following previous vaccinations and/or natural exposures is referred to here as baseline immune history (BIH). To investigate the hypothesis that obesity impacts immune memory to infections and vaccines, we profiled the BIH of obese and healthy-weight adults vaccinated with the 2010-2011 seasonal influenza vaccine in response to conformational and linear antigens. Despite the extensive heterogeneity of the BIH profiles in both groups, there were striking differences between obese and healthy subjects, especially with regard to A/H1N1 strains and the 2009 pandemic virus (Cal09). Individuals with obesity had lower IgG and IgA magnitude and breadth for a panel of A/H1N1 whole viruses and hemagglutinin proteins from 1933 to 2009 but increased IgG magnitude and breadth for linear peptides from the Cal09 H1 and N1 proteins. Age was also associated with A/H1N1 BIH, with young individuals with obesity being more likely to have reduced A/H1N1 BIH. We found that individuals with low IgG BIH had significantly lower neutralizing antibody titers than individuals with high IgG BIH. Taken together, our findings suggest that increased susceptibility of obese participants to influenza infection may be mediated in part by obesity-associated differences in the memory B-cell repertoire, which cannot be ameliorated by current seasonal vaccination regimens. Overall, these data have vital implications for the next generation of influenza virus and SARS-CoV-2 vaccines. IMPORTANCE Obesity is associated with increased morbidity and mortality from influenza and SARS-CoV-2 infection. While vaccination is the most effective strategy for preventing influenza virus infection, our previous studies showed that influenza vaccines fail to provide optimal protection in obese individuals despite reaching canonical correlates of protection. Here, we show that obesity may impair immune history in humans and cannot be overcome by seasonal vaccination, especially in younger individuals with decreased lifetime exposure to infections and seasonal vaccines. Low baseline immune history is associated with decreased protective antibody responses. Obesity potentially handicaps overall responses to vaccination, biasing it toward responses to linear epitopes, which may reduce protective capacity. Taken together, our data suggest that young obese individuals are at an increased risk of reduced protection by vaccination, likely due to altered immune history biased toward nonprotective antibody responses. Given the worldwide obesity epidemic coupled with seasonal respiratory virus infections and the inevitable next pandemic, it is imperative that we understand and improve vaccine efficacy in this high-risk population. The design, development, and usage of vaccines for and in obese individuals may need critical evaluation, and immune history should be considered an alternate correlate of protection in future vaccine clinical trials.https://journals.asm.org/doi/10.1128/spectrum.00010-23antibody repertoireinfluenza vaccinesobesity |
| spellingShingle | Marwa Abd Alhadi Lilach M. Friedman Erik A. Karlsson Liel Cohen-Lavi Anat Burkovitz Stacey Schultz-Cherry Terry L. Noah Samuel S. Weir Lester M. Shulman Melinda A. Beck Tomer Hertz Obesity Is Associated with an Impaired Baseline Repertoire of Anti-Influenza Virus Antibodies Microbiology Spectrum antibody repertoire influenza vaccines obesity |
| title | Obesity Is Associated with an Impaired Baseline Repertoire of Anti-Influenza Virus Antibodies |
| title_full | Obesity Is Associated with an Impaired Baseline Repertoire of Anti-Influenza Virus Antibodies |
| title_fullStr | Obesity Is Associated with an Impaired Baseline Repertoire of Anti-Influenza Virus Antibodies |
| title_full_unstemmed | Obesity Is Associated with an Impaired Baseline Repertoire of Anti-Influenza Virus Antibodies |
| title_short | Obesity Is Associated with an Impaired Baseline Repertoire of Anti-Influenza Virus Antibodies |
| title_sort | obesity is associated with an impaired baseline repertoire of anti influenza virus antibodies |
| topic | antibody repertoire influenza vaccines obesity |
| url | https://journals.asm.org/doi/10.1128/spectrum.00010-23 |
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