Immunogenicity and efficacy of baculovirus-expressed and DNA-based equine influenza virus hemagglutinin vaccines in mice.
Abstract: Two fundamentally different approaches to vaccination of BALB/c mice with the hemagglutinin (HA) of A/Equine/Kentucky/1/81 (H3N8) (Eq/KY) were evaluated, that is, administration of HA protein vs administration of HA-encoding DNA. Each vaccine was tested for its immunogenicity and ability to provide protection from homologous virus challenge. HA protein was synthesized in vitro by infection of Sf21 insect cells with a recombinant baculovirus. Intranasal administration of this vaccine induced virus-specific antibodies, as measured by enzyme-linked immunosorbent assay (ELISA), but did not induce virus neutralizing (VN) antibodies. This route of administration provided partial protection from virus challenge, but interestingly, this protection was completely abrogated, rather than enhanced, by co-administration of 10 micrograms of cholera holotoxin. As a second approach, mice were directly vaccinated in vivo by Accell gene gun delivery of plasmid DNA encoding the Eq/KY HA gene. This approach induced VN antibodies as well as virus-specific ELISA antibodies. When two doses of DNA vaccine were administered 3 weeks apart, mice were not protected from challenge, although they cleared the infection more rapidly than control mice. However, when the second DNA vaccination was delayed until 9 weeks after the first, 9 out of 10 vaccinated mice were completely protected. These results indicate that the time between initial and booster DNA vaccinations may be an important variable in determining DNA vaccination efficacy.
Publication Date: 1997-07-01 PubMed ID: 9269061DOI: 10.1016/s0264-410x(96)00309-xGoogle Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research studied two different methods of vaccinating mice against equine influenza virus with a primary focus on the timing and efficacy of the vaccines. The two mechanisms used were hemagglutinin (HA) protein administered nasally and HA-encoding DNA administered using a gene gun. While both methods stimulated an immune response, the time between the initial and booster DNA vaccinations proved a key factor in determining the effectiveness of the vaccine.
Vaccine Development Approaches
- The research involved using two different methods for vaccination against the equine influenza virus in mice. The virus strain used was A/Equine/Kentucky/1/81 (H3N8), also known as Eq/KY.
- The first method involved the administration of hemagglutinin (HA) protein. This protein, crucial for the virus’s survival and infection, was synthesized in vitro, or outside a living organism, through the infection of insect cells via a recombinant baculovirus.
- The second vaccination approach was the administration of HA-encoding DNA. In this approach, plasmid DNA, carrying the gene for Eq/KY HA, was injected into mice via a gene gun.
Vaccine Immunogenicity and Efficacy
- Both vaccination approaches displayed different levels of immunity induced and protection from infection.
- The intranasal administration of HA protein induced virus-specific antibodies, detectable by enzyme-linked immunosorbent assay (ELISA). However, it didn’t trigger the production of virus neutralizing (VN) antibodies.
- The HA protein vaccine provided partial protection, but interestingly, when combined with cholera holotoxin, this vaccine failed to provide any protection, indicating potential interactive factors.
- On the other hand, the DNA-based vaccine induced not only virus-specific ELISA antibodies but also VN antibodies, suggesting a higher potential for virus neutralization.
- When this DNA vaccine was administered in two doses, three weeks apart, it didn’t completely prevent the infection. However, it seemed to aid in clearing off the infection more quickly than in unvaccinated mice.
Impact of Vaccination Timing
- A key finding from this research was the impact of the timing between the primary and booster doses of the DNA vaccine.
- When the second DNA vaccine was given nine weeks after the first, a significantly higher protection level was noted. This observation suggests that the time interval between initial and booster DNA vaccinations may play an important role in determining the efficacy of DNA vaccines.
- The study concluded that while the HA protein vaccine held potential, the results hinted at a possible influential factor for DNA vaccination success, specifically the spacing of vaccinations.
Cite This Article
APA
Olsen CW, McGregor MW, Dybdahl-Sissoko N, Schram BR, Nelson KM, Lunn DP, Macklin MD, Swain WF, Hinshaw VS.
(1997).
Immunogenicity and efficacy of baculovirus-expressed and DNA-based equine influenza virus hemagglutinin vaccines in mice.
Vaccine, 15(10), 1149-1156.
https://doi.org/10.1016/s0264-410x(96)00309-x Publication
Researcher Affiliations
- Department of Pathobiological Science, School of Veterinary Medicine, University of Wisconsin-Madison 53706, USA.
MeSH Terms
- Adjuvants, Immunologic / administration & dosage
- Animals
- Antibodies, Viral / blood
- Baculoviridae / genetics
- Base Sequence
- Cholera Toxin / administration & dosage
- DNA Primers / genetics
- Hemagglutinins, Viral / genetics
- Hemagglutinins, Viral / immunology
- Immunization Schedule
- Immunization, Secondary
- Influenza A virus / genetics
- Influenza A virus / immunology
- Influenza A virus / isolation & purification
- Influenza Vaccines / administration & dosage
- Influenza Vaccines / genetics
- Influenza Vaccines / pharmacology
- Lung / virology
- Mice
- Mice, Inbred BALB C
- Molecular Sequence Data
- Orthomyxoviridae Infections / immunology
- Orthomyxoviridae Infections / prevention & control
- Orthomyxoviridae Infections / virology
- Polymerase Chain Reaction
- Vaccines, DNA / administration & dosage
- Vaccines, DNA / genetics
- Vaccines, DNA / pharmacology
Citations
This article has been cited 6 times.- Oladunni FS, Oseni SO, Martinez-Sobrido L, Chambers TM. Equine Influenza Virus and Vaccines.. Viruses 2021 Aug 20;13(8).
- Berry JD, Hay K, Rini JM, Yu M, Wang L, Plummer FA, Corbett CR, Andonov A. Neutralizing epitopes of the SARS-CoV S-protein cluster independent of repertoire, antigen structure or mAb technology.. MAbs 2010 Jan-Feb;2(1):53-66.
- van Oers MM. Vaccines for viral and parasitic diseases produced with baculovirus vectors.. Adv Virus Res 2006;68:193-253.
- Leitner WW, Ying H, Restifo NP. DNA and RNA-based vaccines: principles, progress and prospects.. Vaccine 1999 Dec 10;18(9-10):765-77.
- Oxburgh L, Klingeborn B. Cocirculation of two distinct lineages of equine influenza virus subtype H3N8.. J Clin Microbiol 1999 Sep;37(9):3005-9.
- Larsen DL, Dybdahl-Sissoko N, McGregor MW, Drape R, Neumann V, Swain WF, Lunn DP, Olsen CW. Coadministration of DNA encoding interleukin-6 and hemagglutinin confers protection from influenza virus challenge in mice.. J Virol 1998 Feb;72(2):1704-8.
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