Mucosal co-administration of cholera toxin and influenza virus hemagglutinin-DNA in ponies generates a local IgA response.
Abstract: We have previously demonstrated that equine influenza virus hemagglutinin (HA) DNA vaccination protects ponies from challenge infection, and induces protective IgGa and IgGb responses. However, this approach does not induce a nasal IgA response. The objective of this study was to examine the value of cholera toxin (CT) administration as an adjuvant for intranasal HA DNA vaccination, and to measure protection 3 months after DNA vaccination. After an immunogenic dose of CT was determined, ponies were immunized on two occasions by intranasal administration of HA DNA and cholera toxin, or HA DNA alone. Ponies in both groups received two additional HA DNA particle mediated vaccinations at skin and mucosal sites. Antibody responses, and protection from challenge infection 3 months after the last vaccination were studied and compared to an influenza virus naive control group. Ponies in both vaccination groups produced virus-specific IgG antibodies in serum following vaccination and showed clinical protection from challenge infection 3 months after the last vaccination. Co-administration of CT plus HA DNA vaccination induced a nasal IgA response. In addition, analysis of antibody titers in nasal secretions indicated local production of nasal IgGb, which was amplified by CT administration.
Publication Date: 2003-06-12 PubMed ID: 12798652DOI: 10.1016/s0264-410x(03)00161-0Google Scholar: Lookup
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- Comparative Study
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research focuses on the impact of using cholera toxin as an enhancer, in conjunction with the influenza virus DNA vaccination in ponies, with the goal of stirring up a nasal IgA immune response. The study recorded a positive result with the generation of a local IgA response in the ponies, which suggests that a combination of cholera toxin and influenza virus hemagglutinin-DNA could potentially improve the efficacy of the vaccine.
Understanding the Context and Purpose of the Research
- In previous research, equine influenza virus hemagglutinin (HA) DNA vaccination was discovered to be able to protect ponies from associated viral infections. This vaccine stirred up protective IgGa and IgGb responses, two types of antibodies (immune response agents).
- This protection was not accompanied by a nasal IgA response, which led to the question of whether this type of response could be instigated.
- The researchers’ main goal was to investigate the use of cholera toxin (CT) as an adjuvant – a substance that enhances the body’s immune response to a foreign substance (antigen) – for these intranasal HA DNA vaccinations.
Methodology and Procedure of the Research
- An immunogenic dose of CT was determined for the experiment. Following this, the ponies were immunized twice, either with a combination of the HA DNA vaccine and cholera toxin or with the HA DNA vaccine only.
- Ponies from both groups were given two more HA DNA particle-mediated vaccinations at both skin and mucosal locations.
- Subsequent examinations were conducted to assess the varying levels of protection from challenge infection three months after the final vaccination, which were then compared against a control group of influenza virus naive ponies.
Findings and Results of the Research
- The study discovered that ponies in both vaccination groups produced virus-specific IgG antibodies in their serum after being vaccinated, which provided clinical protection from the challenge infection for at least three months after the final vaccination.
- Notably, the use of CT in conjunction with the HA DNA vaccination induced a nasal IgA response in the ponies.
- The study also found that antibody titers in nasal secretions presented evidence of local production of nasal IgGb. This production was amplified by the administration of CT.
Conclusion and Implications of the Research
- The positive findings of this study may offer promising avenues for enhancing the efficacy of the equine influenza virus HA DNA vaccine. The addition of an adjuvant like CT might help to trigger a stronger, more robust immune response, which could potentially result in a more effective and long-lasting vaccination.
Cite This Article
APA
Soboll G, Nelson KM, Leuthner ES, Clark RJ, Drape R, Macklin MD, Swain WF, Olsen CW, Lunn DP.
(2003).
Mucosal co-administration of cholera toxin and influenza virus hemagglutinin-DNA in ponies generates a local IgA response.
Vaccine, 21(21-22), 3081-3092.
https://doi.org/10.1016/s0264-410x(03)00161-0 Publication
Researcher Affiliations
- School of Veterinary Medicine, University of Wisconsin, 2015 Linden Drive West, Madison, WI 53706, USA.
MeSH Terms
- Administration, Intranasal
- Animals
- Antibodies, Viral / blood
- Cholera Toxin / administration & dosage
- Cholera Toxin / immunology
- Female
- Hemagglutinins, Viral / genetics
- Horse Diseases / immunology
- Horse Diseases / prevention & control
- Horse Diseases / virology
- Horses
- Immunity, Mucosal
- Immunoglobulin A / biosynthesis
- Influenza A virus
- Influenza Vaccines / administration & dosage
- Influenza Vaccines / immunology
- Male
- Nasal Mucosa / immunology
- Orthomyxoviridae Infections / immunology
- Orthomyxoviridae Infections / prevention & control
- Orthomyxoviridae Infections / veterinary
- Vaccination / veterinary
- Vaccines, DNA / administration & dosage
- Vaccines, DNA / immunology
Citations
This article has been cited 6 times.- Paillot R. A Systematic Review of Recent Advances in Equine Influenza Vaccination. Vaccines (Basel) 2014 Nov 14;2(4):797-831.
- Ault A, Zajac AM, Kong WP, Gorres JP, Royals M, Wei CJ, Bao S, Yang ZY, Reedy SE, Sturgill TL, Page AE, Donofrio-Newman J, Adams AA, Balasuriya UB, Horohov DW, Chambers TM, Nabel GJ, Rao SS. Immunogenicity and clinical protection against equine influenza by DNA vaccination of ponies. Vaccine 2012 Jun 6;30(26):3965-74.
- Chambers TM, Quinlivan M, Sturgill T, Cullinane A, Horohov DW, Zamarin D, Arkins S, García-Sastre A, Palese P. Influenza A viruses with truncated NS1 as modified live virus vaccines: pilot studies of safety and efficacy in horses. Equine Vet J 2009 Jan;41(1):87-92.
- Mealey RH, Stone DM, Hines MT, Alperin DC, Littke MH, Leib SR, Leach SE, Hines SA. Experimental Rhodococcus equi and equine infectious anemia virus DNA vaccination in adult and neonatal horses: effect of IL-12, dose, and route. Vaccine 2007 Oct 23;25(43):7582-97.
- Quinlivan M, Zamarin D, García-Sastre A, Cullinane A, Chambers T, Palese P. Attenuation of equine influenza viruses through truncations of the NS1 protein. J Virol 2005 Jul;79(13):8431-9.
- Elliott S, Olufemi OT, Daly JM. Systematic Review of Equine Influenza A Virus Vaccine Studies and Meta-Analysis of Vaccine Efficacy. Viruses 2023 Nov 28;15(12).
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