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Intranasal seasonal influenza vaccine and a TLR-3 agonist, rintatolimod, induced cross-reactive IgA antibody formation against avian H5N1 and H7N9 inf

tetano

Editor, Senior Moderator
Vaccine. 2014 Aug 13. pii: S0264-410X(14)01045-7. doi: 10.1016/j.vaccine.2014.07.078. [Epub ahead of print]
Intranasal seasonal influenza vaccine and a TLR-3 agonist, rintatolimod, induced cross-reactive IgA antibody formation against avian H5N1 and H7N9 influenza HA in humans.
Overton ET1, Goepfert PA2, Cunningham P3, Carter WA4, Horvath J5, Young D6, Strayer DR7.
Author information
Abstract

The intranasal use of rintatolimod, a specific TLR-3 agonist, combined with trivalent seasonal influenza vaccine generated cross-protection against highly pathogenic H5N1 avian influenza in mice. The purpose of this clinical trial is to assess the safety and impact of rintatolimod on intranasal influenza vaccine in healthy adults. During Stage I of this Phase I/II clinical trial, 12 volunteers were immunized intranasally with 3 doses of FluMist? seasonal influenza vaccine on Days 0, 28, and 56 followed by intranasal rintatolimod (50μg, 200μg, or 500μg) 3 days later. Parotid saliva and nasal wash samples were collected at baseline on Days 25, 53, 84, and 417. The samples were tested for IgA and IgG specific antibodies (Ab) directed against the homologous FluMist? viral hemagglutinins (HAs). In addition, viral specific responses against influenza A HAs were tested for IgA Ab cross-reactivity against 3 H5 clades: HA (H5N1) A/Indonesia/5/2005, HA (H5N1) A/Hong Kong/483/97 and HA (H5N1) A/Vietnam/1194/2004, as well as, two H7 strains, HA (H7N9) A/Shanghai/2/2013 and HA (H7N3) A/chicken/Jalisco/CPA1. The combination of the intranasal FluMist? along with the rintatolimod generated specific secretory IgA responses of at least 4-fold over baseline against at least one of the homologous vaccine strains included in the vaccine in 92% of the vaccines. Additionally, this vaccination strategy induced cross-reactive secretory IgA against highly pathogenic avian influenza virus strains H5N1, H7N9, and H7N3 with pandemic potential for humans. The combination of rintatolimod and FluMist? was well-tolerated.

Copyright ? 2014 Elsevier Ltd. All rights reserved.
KEYWORDS:

Adjuvant; Influenza; LAIV; Live attenuated influenza vaccine; Mucosal IgA; TLR-3

PMID:
25128802
[PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/pubmed/25128802
 
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