ABSTRACT
Antigen-specific mucosal immunity is thought to be important for protection against influenza virus infection. Currently licensed parenteral influenza vaccines stimulate the production of serum antibodies, but are poor inducers of mucosal immunity. The adjuvant MF59 has been shown to enhance the humoral immune response to parenteral influenza vaccine in humans and the mucosal immune response to intranasally-administered influenza vaccine in mice. We conducted an open-label safety study followed by an observer-blind, randomized trial comparing the immune response to intranasally-administered subunit influenza vaccine adjuvanted with MF59, unadjuvanted subunit influenza vaccine, and placebo. Adverse reactions did not occur significantly more frequently in vaccinees than placebo recipients. Of 31 subjects receiving 2 doses of MF59-adjuvanted influenza vaccine, 19 (61%), 8 (26%), and 11 (35%) developed a mucosal IgA response to influenza A/H1N1, A/H3N2, and B, respectively. The percentage of subjects with a serum antibody response was slightly lower. The immune responses to adjuvanted vaccine were not significantly different from those to unadjuvanted vaccine. Both vaccines gave more frequent responses than seen in placebo recipients, indicating the potential of intranasal inactivated vaccines to stimulate local IgA responses.
Subject(s)
Adjuvants, Immunologic/administration & dosage , Influenza Vaccines/administration & dosage , Polysorbates/administration & dosage , Squalene/administration & dosage , Administration, Intranasal , Adolescent , Adult , Hemagglutination Inhibition Tests , Humans , Immunoglobulin A, Secretory/biosynthesis , Influenza Vaccines/adverse effects , Influenza Vaccines/immunologyABSTRACT
Intranasal trivalent, cold-adapted, live attenuated influenza vaccine (CAIV-T) is a promising alternative to inactivated vaccine for protection against influenza in children. However, correlates of immunity are not well defined. To determine the mucosal immune response to CAIV-T, 19 children ages 15-55 months were randomized to receive two doses of CAIV-T or placebo. Influenza-specific IgA to the haemagglutinin of each of three contemporary strains was measured in nasal washes collected pre- and postvaccination using a kinetic enzyme-linked immunosorbent assay. After two doses of study drug, 62, 69 and 85% of CAIV-T recipients demonstrated a mucosal IgA response to influenza A/H1N1, A/H3N2, and B strains respectively; in comparison, 33, 0 and 17% of placebo recipients demonstrated an IgA response to the same strains (p = 0.35, 0.01 and 0.01). Overall, seropositive vaccinees were 4.5 times more likely to develop a mucosal immune response than an HAI response (p = 0.015). Two doses of CAIV-T induce a mucosal IgA response to all three influenza vaccine antigens in the majority of children. In addition, a mucosal antibody response may be the only indication of a vaccine take in a seropositive child.
Subject(s)
Antibodies, Viral/analysis , Influenza Vaccines/immunology , Orthomyxoviridae/immunology , Administration, Intranasal , Child, Preschool , Enzyme-Linked Immunosorbent Assay , Hemagglutination Inhibition Tests , Humans , Immunity, Mucosal , Immunoglobulin A, Secretory/analysis , Infant , Influenza Vaccines/administration & dosage , Sensitivity and Specificity , Vaccines, Attenuated/immunologyABSTRACT
Neutralization and indirect immunofluorescence were compared for the identification and serotyping of poliovirus. Indirect immunofluorescence was highly concordant with neutralization and offers a more rapid procedure for identification and characterization of poliovirus strains.
Subject(s)
Feces/virology , Poliomyelitis/diagnosis , Poliovirus/isolation & purification , Fluorescent Antibody Technique , Humans , Neutralization TestsABSTRACT
Seroresponses to trivalent oral poliovirus vaccine are not uniform throughout the world. Definition of the variables that determine successful immunization is vital to ensure global polio eradication. One such variable may be dosage interval. To investigate this effect 108 infants were enrolled in a clinical trial and randomly assigned to receive three doses of trivalent oral poliovirus vaccine (standard United States formulation) at 2, 3 and 4 or 2, 4 and 6 months of age. After three doses of vaccine given before 6 months of age, immunity was virtually complete for each of the three poliovirus types in both groups. After two doses the seroresponse rate to each type was less with the shorter dose interval. However the difference was not significant (P = 0.15) in the sample size studied. Such responses differ markedly from those seen in developing countries, where four or more doses of vaccine may fail to provide complete protection. Differences other than dosage interval must contribute to those failures.
Subject(s)
Antibodies, Viral/biosynthesis , Poliovirus Vaccine, Oral/administration & dosage , Poliovirus Vaccine, Oral/immunology , Vaccination , Dose-Response Relationship, Drug , Feces/virology , Humans , Immunization Schedule , Infant , Poliomyelitis/immunology , Poliomyelitis/prevention & control , Poliovirus/immunology , Poliovirus/isolation & purification , Virus SheddingABSTRACT
From January to July 1991, an outbreak of mumps occurred in Maury County, Tennessee. At the primarily affected high school, where 98% of students and all but 1 student with mumps had been vaccinated before the outbreak, 68 mumps cases occurred among 1116 students (attack rate, 6.1%). Students vaccinated before 1988 (the first year mumps vaccination was required for school attendance in Tennessee) may have been at greater risk of mumps than those vaccinated later (65[6.1%] of 1001 vs. 2[2.2%] of 89; risk ratio, 2.9; 95% confidence interval, 0.7-11.6). Of 13 persons with confirmed mumps who underwent serologic testing, 3 lacked IgM antibody in well-timed acute- and convalescent-phase serum specimens. Vaccine failure accounted for a sustained mumps outbreak in a highly vaccinated population. Most mumps cases were attributable to primary vaccine failure. It is possible that waning vaccine-induced immunity also played a role.