Inclusion of Flagellin during Vaccination against Influenza Enhances Recall Responses in Nonhuman Primate Neonates
| Autor: | Steven B. Mizel, Kristina De Paris, Ralph B. D'Agostino, Lance K. Blevins, Sarah L. Hayward, Griffith D. Parks, Martha A. Alexander-Miller, Nancy D. Kock, Beth C. Holbrook, Jong R. Kim, S. Tyler Aycock, Matthew J. Jorgensen |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Influenza vaccine
T-Lymphocytes medicine.medical_treatment Immunology Population Biology Antibodies Viral Microbiology Virus Immune system Adjuvants Immunologic Orthomyxoviridae Infections Virology Chlorocebus aethiops Vaccines and Antiviral Agents medicine Animals education education.field_of_study Vaccination Disease Models Animal Animals Newborn Vaccines Inactivated Influenza Vaccines TLR5 Immunoglobulin G Insect Science biology.protein Adjuvant Flagellin |
| DOI: | 10.17615/041d-s909 |
| Popis: | Influenza virus can cause life-threatening infections in neonates and young infants. Although vaccination is a major countermeasure against influenza, current vaccines are not approved for use in infants less than 6 months of age, in part due to the weak immune response following vaccination. Thus, there is a strong need to develop new vaccines with improved efficacy for this vulnerable population. To address this issue, we established a neonatal African green monkey (AGM) nonhuman primate model that could be used to identify effective influenza vaccine approaches for use in young infants. We assessed the ability of flagellin, a Toll-like receptor 5 (TLR5) agonist, to serve as an effective adjuvant in this at-risk population. Four- to 6-day-old AGMs were primed and boosted with inactivated PR8 influenza virus (IPR8) adjuvanted with either wild-type flagellin or inactive flagellin with a mutation at position 229 (m229), the latter of which is incapable of signaling through TLR5. Increased IgG responses were observed following a boost, as well as at early times after challenge, in infants vaccinated with flagellin-adjuvanted IPR8. Inclusion of flagellin during vaccination also resulted in a significantly increased number of influenza virus-specific T cells following challenge compared to the number in infants vaccinated with the m229 adjuvant. Finally, following challenge infants vaccinated with IPR8 plus flagellin exhibited a reduced pathology in the lungs compared to that in infants that received IPR8 plus m229. This study provides the first evidence of flagellin-mediated enhancement of vaccine responses in nonhuman primate neonates. IMPORTANCE Young infants are particularly susceptible to severe disease as a result of influenza virus infection. Compounding this is the lack of effective vaccines for use in this vulnerable population. Here we describe a vaccine approach that results in improved immune responses and protection in young infants. Incorporation of flagellin during vaccination resulted in increased antibody and T cell responses together with reduced disease following virus infection. These results suggest that flagellin may serve as an effective adjuvant for vaccines targeted to this vulnerable population. |
| Databáze: | OpenAIRE |
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