Antigen-specific immunoglobulin variable region sequencing measures humoral immune response to vaccination in the equine neonate.
Abstract: The value of prophylactic neonatal vaccination is challenged by the interference of passively transferred maternal antibodies and immune competence at birth. Taken our previous studies on equine B cell ontogeny, we hypothesized that the equine neonate generates a diverse immunoglobulin repertoire in response to vaccination, independently of circulating maternal antibodies. In this study, equine neonates were vaccinated with 3 doses of keyhole limpet hemocyanin (KLH) or equine influenza vaccine, and humoral immune responses were assessed using antigen-specific serum antibodies and B cell Ig variable region sequencing. An increase (p<0.0001) in serum KLH-specific IgG level was measured between days 21 and days 28, 35 and 42 in vaccinated foals from non-vaccinated mares. In vaccinated foals from vaccinated mares, serum KLH-specific IgG levels tended to increase at day 42 (p = 0.07). In contrast, serum influenza-specific IgG levels rapidly decreased (p≤0.05) in vaccinated foals from vaccinated mares within the study period. Nevertheless, IGHM and IGHG sequences were detected in KLH- and influenza- sorted B cells of vaccinated foals, independently of maternal vaccination status. Immunoglobulin nucleotide germline identity, IGHV gene usage and CDR length of antigen-specific IGHG sequences in B cells of vaccinated foals revealed a diverse immunoglobulin repertoire with isotype switching that was comparable between groups and to vaccinated mares. The low expression of CD27 memory marker in antigen-specific B cells, and of cytokines in peripheral blood mononuclear cells upon in vitro immunogen stimulation indicated limited lymphocyte population expansion in response to vaccine during the study period.
Publication Date: 2017-05-16 PubMed ID: 28520789PubMed Central: PMC5433778DOI: 10.1371/journal.pone.0177831Google Scholar: Lookup
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Summary
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This research investigates the immune response in newborn horses in relation to vaccinations, considering the possible interference from maternal antibodies. The study shows that newborn horses generate a diverse range of immunoglobulins in response to vaccinations, regardless of maternal antibodies, proving the value of neonatal vaccination.
Study Background
- The purpose of this study was to investigate the effects of neonatal vaccination on the immune response of newborn horses, also known as foals. Vaccinating neonates can be a valuable preventive measure, but the presence of maternal antibodies transferred passively to the offspring can interfere with this process.
- The researchers had previously studied B cell ontogeny (development) in horses, which led them to hypothesize that the equine neonate generates a diverse immunoglobulin (a type of protein that functions as an antibody) repertoire in response to vaccination, irrespective of circulating maternal antibodies.
Methods and Procedures
- The researchers vaccinated equine neonates with three doses of keyhole limpet hemocyanin (KLH) or equine influenza vaccine, both are commonly used to stimulate immune response in research.
- They then assessed the humoral immune response (the part of the immune system that involves antibodies) using antigen-specific serum antibodies and B cell immunoglobulin (Ig) variable region sequencing, a method used to analyze the antibody repertoire and identify specific immune response patterns.
Results
- The study identified an increase in serum KLH-specific IgG level between certain days post vaccination in foals born from non-vaccinated mares. Meanwhile, for foals from vaccinated mares, IgG levels tended to increase at a later point.
- In contrast, foals from vaccinated mares showed a rapid decrease in serum influenza-specific IgG levels within the study period.
- In spite of maternal vaccination status, IGHM and IGHG sequences were detected in KLH- and influenza- sorted B cells of vaccinated foals, indicating that neonatal vaccination produced a unique immune response.
- Foals also showed a diverse immunoglobulin repertoire with isotype switching that was similar among groups and comparable to vaccinated mares.
Limitations and Future Research
- The study found limited lymphocyte population expansion in response to vaccine during the study period, underlined by the low expression of CD27 memory marker in antigen-specific B cells, and of cytokines in peripheral blood mononuclear cells upon in vitro immunogen stimulation.
- This may suggest that the neonate’s immune system is still developing and may respond differently to vaccinations compared to the mature immune system. Further research in this area, potentially over a more extended period or with different vaccination strategies, could yield more information about the optimal timing and procedures for equine neonate vaccination.
Cite This Article
APA
Tallmadge RL, Miller SC, Parry SA, Felippe MJB.
(2017).
Antigen-specific immunoglobulin variable region sequencing measures humoral immune response to vaccination in the equine neonate.
PLoS One, 12(5), e0177831.
https://doi.org/10.1371/journal.pone.0177831 Publication
Researcher Affiliations
- Equine Immunology Laboratory, Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
- Equine Immunology Laboratory, Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
- Cornell Statistical Consulting Unit, Cornell University, Ithaca, New York, United States of America.
- Equine Immunology Laboratory, Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
MeSH Terms
- Animals
- Animals, Newborn
- B-Lymphocytes / immunology
- Female
- Hemocyanins / immunology
- Horse Diseases / immunology
- Horse Diseases / prevention & control
- Horses / immunology
- Humans
- Immunity, Humoral
- Immunoglobulin Variable Region / blood
- Immunoglobulin Variable Region / chemistry
- Immunoglobulin Variable Region / immunology
- Male
- Orthomyxoviridae Infections / immunology
- Orthomyxoviridae Infections / prevention & control
- Orthomyxoviridae Infections / veterinary
- Vaccination / methods
- Vaccination / veterinary
Conflict of Interest Statement
The authors have declared that no competing interests exist.
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Citations
This article has been cited 2 times.- Wibmer CK, Mashilo P. Exploiting V-Gene Bias for Rapid, High-Throughput Monoclonal Antibody Isolation from Horses.. Viruses 2022 Sep 30;14(10).
- Tallmadge RL, Wang M, Sun Q, Felippe MJB. Transcriptome analysis of immune genes in peripheral blood mononuclear cells of young foals and adult horses.. PLoS One 2018;13(9):e0202646.
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