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Localized mucosal response to intranasal live attenuated influenza vaccine in adults.

Abstract

BACKGROUND

Influenza virus infection is a major public health burden worldwide. Available vaccines include the inactivated intramuscular trivalent vaccine and, more recently, an intranasal live attenuated influenza vaccine (LAIV). The measure of successful vaccination with the inactivated vaccine is a systemic rise in immunoglobulin G (IgG) level, but for the LAIV no such correlate has been established.

METHODS

Seventy-nine subjects were given the LAIV FluMist. Blood was collected prior to vaccination and 3 days and 30 days after vaccination. Nasal wash was collected 3 days and 30 days after vaccination. Responses were measured systemically and in mucosal secretions for cytokines, cell activation profiles, and antibody responses.

RESULTS

Only 9% of subjects who received LAIV seroconverted, while 33% of patients developed at least a 2-fold increase in influenza virus-specific immunoglobulin A (IgA) antibodies in nasal wash. LAIV induced a localized inflammation, as suggested by increased expression of interferon-response genes in mucosal RNA and increased granulocyte colony-stimulating factor (G-CSF) and IP-10 in nasal wash. Interestingly, patients who seroconverted had significantly lower serum levels of G-CSF before vaccination.

CONCLUSIONS

Protection by LAIV is likely provided through mucosal IgA and not by increases in systemic IgG. LAIV induces local inflammation. Seroconversion is achieved in a small fraction of subjects with a lower serum G-CSF level.

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  • Authors+Show Affiliations

    ,

    Department of Microbiology, Mount Sinai School of Medicine, New York, New York 10029, USA.

    , , , , , , ,

    Source

    The Journal of infectious diseases 207:1 2013 Jan 01 pg 115-24

    MeSH

    Administration, Intranasal
    Adolescent
    Adult
    Animals
    Antibodies, Viral
    Cohort Studies
    Cytokines
    Dogs
    Female
    Hemagglutinin Glycoproteins, Influenza Virus
    Humans
    Immunity, Mucosal
    Immunoglobulin A
    Influenza A Virus, H1N1 Subtype
    Influenza A Virus, H3N2 Subtype
    Influenza B virus
    Influenza Vaccines
    Influenza, Human
    Madin Darby Canine Kidney Cells
    Male
    Middle Aged
    Nasal Lavage Fluid
    Vaccination
    Vaccines, Attenuated
    Vaccines, Inactivated
    Young Adult

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural

    Language

    eng

    PubMed ID

    23087433

    Citation

    Barría, Maria Ines, et al. "Localized Mucosal Response to Intranasal Live Attenuated Influenza Vaccine in Adults." The Journal of Infectious Diseases, vol. 207, no. 1, 2013, pp. 115-24.
    Barría MI, Garrido JL, Stein C, et al. Localized mucosal response to intranasal live attenuated influenza vaccine in adults. J Infect Dis. 2013;207(1):115-24.
    Barría, M. I., Garrido, J. L., Stein, C., Scher, E., Ge, Y., Engel, S. M., ... Moran, T. M. (2013). Localized mucosal response to intranasal live attenuated influenza vaccine in adults. The Journal of Infectious Diseases, 207(1), pp. 115-24. doi:10.1093/infdis/jis641.
    Barría MI, et al. Localized Mucosal Response to Intranasal Live Attenuated Influenza Vaccine in Adults. J Infect Dis. 2013 Jan 1;207(1):115-24. PubMed PMID: 23087433.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Localized mucosal response to intranasal live attenuated influenza vaccine in adults. AU - Barría,Maria Ines, AU - Garrido,Jose Luis, AU - Stein,Cheryl, AU - Scher,Erica, AU - Ge,Yongchao, AU - Engel,Stephanie M, AU - Kraus,Thomas A, AU - Banach,David, AU - Moran,Thomas M, Y1 - 2012/10/19/ PY - 2012/10/23/entrez PY - 2012/10/23/pubmed PY - 2013/3/1/medline SP - 115 EP - 24 JF - The Journal of infectious diseases JO - J. Infect. Dis. VL - 207 IS - 1 N2 - BACKGROUND: Influenza virus infection is a major public health burden worldwide. Available vaccines include the inactivated intramuscular trivalent vaccine and, more recently, an intranasal live attenuated influenza vaccine (LAIV). The measure of successful vaccination with the inactivated vaccine is a systemic rise in immunoglobulin G (IgG) level, but for the LAIV no such correlate has been established. METHODS: Seventy-nine subjects were given the LAIV FluMist. Blood was collected prior to vaccination and 3 days and 30 days after vaccination. Nasal wash was collected 3 days and 30 days after vaccination. Responses were measured systemically and in mucosal secretions for cytokines, cell activation profiles, and antibody responses. RESULTS: Only 9% of subjects who received LAIV seroconverted, while 33% of patients developed at least a 2-fold increase in influenza virus-specific immunoglobulin A (IgA) antibodies in nasal wash. LAIV induced a localized inflammation, as suggested by increased expression of interferon-response genes in mucosal RNA and increased granulocyte colony-stimulating factor (G-CSF) and IP-10 in nasal wash. Interestingly, patients who seroconverted had significantly lower serum levels of G-CSF before vaccination. CONCLUSIONS: Protection by LAIV is likely provided through mucosal IgA and not by increases in systemic IgG. LAIV induces local inflammation. Seroconversion is achieved in a small fraction of subjects with a lower serum G-CSF level. SN - 1537-6613 UR - https://www.unboundmedicine.com/medline/citation/23087433/Localized_mucosal_response_to_intranasal_live_attenuated_influenza_vaccine_in_adults_ L2 - https://academic.oup.com/jid/article-lookup/doi/10.1093/infdis/jis641 DB - PRIME DP - Unbound Medicine ER -