title: Evaluation of two live attenuated cold-adapted H5N1 influenza virus vaccines in healthy adults.
abstract: BACKGROUND
  Development of live attenuated influenza vaccines (LAIV) against avian viruses with pandemic potential is an important public health strategy.
  
  
  RESULTS
  We performed open-label trials to evaluate the safety, infectivity, and immunogenicity of H5N1 VN 2004 AA ca and H5N1 HK 2003 AA ca. Each of these vaccines contains a modified H5 hemagglutinin and unmodified N1 neuraminidase from the respective wild-type (wt) parent virus and the six internal protein gene segments of the A/Ann Arbor/6/60 cold-adapted (ca) master donor virus. The H5N1 VN 2004 AA ca vaccine virus was evaluated at dosages of 10(6.7) TCID(50) and 10(7.5) TCID(50), and the H5N1 HK 2003 AA ca vaccine was evaluated at a dosage of 10(7.5) TCID(50). Two doses were administered intranasally to healthy adults in isolation at 4-8 week intervals. Vaccine safety was assessed through daily examinations and infectivity was assessed by viral culture and by realtime reverse transcription-polymerase chain reaction testing of nasal wash (NW) specimens. Immunogenicity was assessed by measuring hemagglutination-inhibition (HI) antibodies, neutralizing antibodies, and IgG or IgA antibodies to recombinant (r)H5 VN 2004 hemagglutinin (HA) in serum or NW. Fifty-nine participants were enrolled: 21 received 10(6.7) TCID(50) and 21 received 10(7.5) TCID(50) of H5N1 VN 2004 AA ca and 17 received H5N1 HK 2003 AA ca. Shedding of vaccine virus was minimal, as were HI and neutralizing antibody responses. Fifty-two percent of recipients of 10(7.5) TCID(50) of H5N1 VN 2004 AA ca developed a serum IgA response to rH5 VN 2004 HA.
  
  
  CONCLUSIONS
  The live attenuated H5N1 VN 2004 and HK 2003 AA ca vaccines bearing avian H5 HA antigens were very restricted in replication and were more attenuated than seasonal LAIV bearing human H1, H3 or B HA antigens. The H5N1 AA ca LAIV elicited serum ELISA antibody but not HI or neutralizing antibody responses in healthy adults. (ClinicalTrials.gov Identifiers: NCT00347672 and NCT00488046).
authors.affiliation: Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, United States. rkarron@jhsph.edu
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Karron
authors.forename: Kawsar
authors.initials: K
authors.lastname: Talaat
authors.forename: Catherine
authors.initials: C
authors.lastname: Luke
authors.forename: Karen
authors.initials: K
authors.lastname: Callahan
authors.forename: Bhagvanji
authors.initials: B
authors.lastname: Thumar
authors.forename: Susan
authors.initials: S
authors.lastname: Dilorenzo
authors.forename: Josephine
authors.initials: J
authors.lastname: McAuliffe
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Schappell
authors.forename: Amorsolo
authors.initials: A
authors.lastname: Suguitan
authors.forename: Kimberly
authors.initials: K
authors.lastname: Mills
authors.forename: Grace
authors.initials: G
authors.lastname: Chen
authors.forename: Elaine
authors.initials: E
authors.lastname: Lamirande
authors.forename: Kathleen
authors.initials: K
authors.lastname: Coelingh
authors.forename: Hong
authors.initials: H
authors.lastname: Jin
authors.forename: Brian R
authors.initials: BR
authors.lastname: Murphy
authors.forename: George
authors.initials: G
authors.lastname: Kemble
authors.forename: Kanta
authors.initials: K
authors.lastname: Subbarao
mesh_terms: D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000032:analysis / Q000097:blood; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007117:Immunization, Secondary / Q000379:methods; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000097:blood; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000009:adverse effects* / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000276:immunology / Q000821:virology; D009500:Neutralization Tests; D014613:Vaccines, Attenuated / Q000009:adverse effects / Q000276:immunology; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D014613:Vaccines, Attenuated