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Evaluation of synthetic infection-enhancing lipopeptides as adjuvants for a live-attenuated canine distemper virus vaccine administered intra-nasally to ferrets
- Source :
- Vaccine, 30(34), 5073-5080. Elsevier
- Publication Year :
- 2012
- Publisher :
- Elsevier, 2012.
-
Abstract
- Background Inactivated paramyxovirus vaccines have been associated with hypersensitivity responses upon challenge infection. For measles and canine distemper virus (CDV) safe and effective live-attenuated virus vaccines are available, but for human respiratory syncytial virus and human metapneumovirus development of such vaccines has proven difficult. We recently identified three synthetic bacterial lipopeptides that enhance paramyxovirus infections in vitro, and hypothesized these could be used as adjuvants to promote immune responses induced by live-attenuated paramyxovirus vaccines. Methods Here, we tested this hypothesis using a CDV vaccination and challenge model in ferrets. Three groups of six animals were intra-nasally vaccinated with recombinant (r) CDV5804PL(CCEGFPC) in the presence or absence of the infection-enhancing lipopeptides Pam3CSK4 or PHCSK4. The recombinant CDV vaccine virus had previously been described to be over-attenuated in ferrets. A group of six animals was mock-vaccinated as control. Six weeks after vaccination all animals were challenged with a lethal dose of rCDV strain Snyder-Hill expressing the red fluorescent protein dTomato. Results Unexpectedly, intra-nasal vaccination of ferrets with rCDV5804PL(CCEGFPC) in the absence of lipopeptides resulted in good immune responses and protection against lethal challenge infection. However, in animals vaccinated with lipopeptide-adjuvanted virus significantly higher vaccine virus loads were detected in nasopharyngeal lavages and peripheral blood mononuclear cells. In addition, these animals developed significantly higher CDV neutralizing antibody titers compared to animals vaccinated with non-adjuvanted vaccine. Conclusions This study demonstrates that the synthetic cationic lipopeptides Pam3CSK4 and PHCSK4 not only enhance paramyxovirus infection in vitro, but also in vivo. Given the observed enhancement of immunogenicity their potential as adjuvants for other live-attenuated paramyxovirus vaccines should be considered.
- Subjects :
- viruses
medicine.medical_treatment
Drug Evaluation, Preclinical
Antibodies, Viral
Transfection
Vaccines, Attenuated
Virus
Microbiology
chemistry.chemical_compound
Lipopeptides
Adjuvants, Immunologic
SDG 3 - Good Health and Well-being
Neutralization Tests
Chlorocebus aethiops
medicine
Cationic Lipopeptides
Animals
Lymphocytes
Distemper
Neutralizing antibody
Distemper Virus, Canine
Vero Cells
Administration, Intranasal
Vaccines, Synthetic
General Veterinary
General Immunology and Microbiology
biology
Canine distemper
Immunogenicity
Public Health, Environmental and Occupational Health
Ferrets
virus diseases
Lipopeptide
Viral Vaccines
Viral Load
medicine.disease
Virology
Antibodies, Neutralizing
Vaccination
Infectious Diseases
chemistry
biology.protein
Molecular Medicine
Female
Adjuvant
Subjects
Details
- ISSN :
- 18732518 and 0264410X
- Volume :
- 30
- Issue :
- 34
- Database :
- OpenAIRE
- Journal :
- Vaccine
- Accession number :
- edsair.doi.dedup.....5058a6762c6fb0b1a797da13f9fca2a6