A dose–response evaluation of inactivated influenza vaccine given intranasally and intramuscularly to healthy young adults

Abstract

Epidemic influenza occurs annually throughout the world and is accompanied by excess morbidity and mortality. Increasing the antigen content and topical administration of vaccine are two strategies being explored to improve the immune responses to trivalent inactivated influenza vaccine (TIV). We conducted a randomized, double-blind, placebo-controlled trial to compare the immunogenicity and reactogenicity of intramuscular (IM), intranasal (IN), or combined IM and IN administration of a contemporary US vaccine formulation at escalating dosage levels in young healthy adults. Two hundred forty three healthy adults between the ages of 18 and 45 years received 15, 30, or 60mcg of trivalent inactivated influenza vaccine by either IN, IM or both routes, 120mcg of vaccine IM, or placebo IN and IM. All dosages and routes of vaccine administration were well-tolerated. A bad taste and mild nasal discomfort were more likely to be reported when influenza vaccine was administered IN, while arm tenderness was more common after IM administration. Significant increases in geometric mean serum antibody titers in both HAI and Nt assays were seen in all of the groups receiving influenza vaccine for all test antigens (P<or=.025, paired t-test), except for the B HAI antibody titer in the group that received 30mcg IN (P=.055, paired t-test). Postvaccination geometric mean serum antibody titers, the frequency of seroresponses, and the percentage achieving postvaccination serum HAI antibody titers of >or=32 were higher following delivery of the study vaccines by an IM route than by the IN route, but significant increases in serum antibody were seen after IN vaccination. Nasal IgA antibody responses were more common when vaccine was administered IN; and, when the IN dosage was increased, the primary benefit from IN vaccine over IM vaccine appeared to be greater induction of nasal secretory antibody.

Recombinant Parainfluenza Virus 5 Vaccine Encoding the Influenza Virus Hemagglutinin Protects against H5N1 Highly Pathogenic Avian Influenza Virus Infection following Intranasal or Intramuscular Vaccination of BALB/c Mice

“…Intranasal administration of inactivated vaccine was associated with increases in IgA in nasal secretions, with increased rates of IgA being associated with i.n. antigen dose (46). In humans, both serum antibody and nasal IgG or IgA have been associated with protection from influenza virus infection (30).…”

Intranasal Immunization of Ferrets with Commercial Trivalent Influenza Vaccines Formulated in a Nanoemulsion-Based Adjuvant

“…versus i.m. administration is the induction of nasal secretory antibody, an important defense against respiratory infections (1).…”

Cross-Reactive Influenza-Specific Antibody-Dependent Cellular Cytotoxicity Antibodies in the Absence of Neutralizing Antibodies

“…Although seasonally influenza virus infection can be prevented through vaccination, the effectiveness of this strategy is limited by the emergence of variant viruses resistant to Ab-mediated neutralization (2)(3)(4). Vaccination with trivalent influenza vaccines (comprising split inactivated preparations of appropriate H1N1, H3N2, and type B virus strains) primarily induces protective hemagglutinin (HA)-specific neutralizing Abs (5,6). However, influenza surface HA proteins are highly susceptible to mutations, leading to loss of immune recognition overtime (antigenic drift), and therefore are required to be generated yearly (7,8).…”