title: An open-label comparison of the immunogenicity and tolerability of intranasal and intramuscular formulations of virosomal influenza vaccine in healthy adults.
abstract: BACKGROUND
  Many intramuscular inactivated influenza vaccines achieve suboptimal results in the prevention of respiratory disease and influenza complications. This has led to the current interest in developing effective oral or intranasal preparations.
  
  
  OBJECTIVE
  This study compared the immunogenicity and tolerability of intranasal and intramuscular formulations of virosomal subunit influenza vaccine in healthy adults. It also assessed the immunogenicity and tolerability of 3 different production lots of the intranasal vaccine containing Escherichia coli heat-labile toxin adjuvant.
  
  
  METHODS
  This was a multicenter, Phase I, randomized, open-label pilot study in which the primary end point was immunogenicity (hemagglutination-inhibition [HI] antibody assay on days 1 and 29). The secondary end point was the frequency of adverse events (AEs). Subjects were assigned to 4 vaccination groups: groups AI, AII, and AIII received intranasal influenza vaccine from batches that differed in the hemagglutinin and neuraminidase strains used, and group B received intramuscular virosomal subunit vaccine. Assessments of health status, hematology, biochemistry, body temperature, heart rate, blood pressure, and incidence of AEs were made on days 1, 8, and 29, and serology was assessed on days 1 and 29.
  
  
  RESULTS
  The study enrolled 88 subjects. All 3 production lots of intranasal vaccine induced an immune response to most of the viral strains administered (A/Singapore, A/Texas, A/Wuhan, B/Beijing), with no notable immunogenic differences between lots. After intranasal vaccination, geometric mean titers (GMT) increased 2.7-fold against A/Singapore (group AI); 1.8- and 3.1-fold against A/Texas (groups AII and AIII, respectively); 1.9- to 2.4-fold against A/Wuhan; and 1.5- to 1.7-fold against B/Beijing. After intramuscular vaccination. GMT increased 11.3-, 6.3-, and 2.7-fold against A/Texas, A/Wuhan, and B/Beijing, respectively. Seroprotection (HI antibody titers > or = 1:40 in > 70% of those vaccinated) was achieved against all strains in the group that received intramuscular vaccination, against A/Wuhan in all groups that received intranasal vaccination, and against A/Texas in group AII. Both vaccine formulations were well tolerated. Intranasal vaccination was associated with a low incidence ( < 20%) of nasal AEs.
  
  
  CONCLUSIONS
  Both the intranasal and intramuscular vaccinations elicited a systemic immune response and were well tolerated. The different batches of intranasal vaccine showed a similar immunogenic profile. Intranasal administration may be preferred to intramuscular administration by some patients.
authors.affiliation: Istituto di Farmacologia II, Facoltà di Medicina e Chirurgia, Università degli Studi di Pavia, Italy.
authors.forename: BernardidiValserraM
authors.initials: B
authors.lastname: de
authors.forename: Alessandro
authors.initials: A
authors.lastname: Zanasi
authors.forename: Salvatore
authors.initials: S
authors.lastname: Ragusa
authors.forename: Reinhard
authors.initials: R
authors.lastname: Glück
authors.forename: Christian
authors.initials: C
authors.lastname: Herzog
mesh_terms: D000281:Administration, Intranasal; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000914:Antibodies, Viral / Q000032:analysis; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D009980:Influenza A virus / Q000276:immunology; D009981:Influenza B virus / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D007273:Injections, Intramuscular; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines