RESUMO
STUDY OBJECTIVES: To evaluate the safety of, and mucosal and systemic immune responses induced by two influenza virus vaccine regimens in subjects with COPD. DESIGN: Single-center, blinded, randomized, prospective clinical trial evaluating two vaccine regimens. SETTING: Outpatient clinics of St. Louis Department of Veterans Affairs Medical Center. PARTICIPANTS: Volunteers (age range, 42 to 88 years) had preexisting COPD with severe obstruction to airflow on average, were male, and were not receiving immunosuppressive medication. INTERVENTIONS: Twenty-nine volunteers were randomly assigned to receive either bivalent live attenuated influenza A virus vaccine (CAV) or saline solution placebo intranasally. All subjects also received an i.m. injection of trivalent inactivated influenza virus vaccine (TVV) simultaneously. MEASUREMENTS AND RESULTS: Clinical status and pulmonary function measured by spirometry did not change significantly after vaccination. Using hemagglutinins (H1 and H3 HA) which more closely resembled those in CAV, mean levels of anti-HA immunoglobulin A (IgA) antibodies in nasal washings increased significantly after vaccination with CAV and TVV compared to prevaccination, but they did not increase significantly after TVV and intranasal placebo. Mean levels of influenza A virus-stimulated interleukin-2 and -4 produced by peripheral blood mononuclear cells in vitro increased significantly after administration of the combination vaccine regimen and to a lesser extent after TVV and intranasal placebo compared to respective prevaccination levels. The timing of the cytokine response appeared different following CAV and TVV compared to TVV and intranasal placebo. CONCLUSIONS: Intranasally administered CAV was safe when given with i.m. administered TVV and there may be an immunologic advantage to administration of the combination vaccine regimen compared to TVV with intranasal placebo.
Assuntos
Vírus da Influenza A/imunologia , Vacinas contra Influenza/administração & dosagem , Influenza Humana/prevenção & controle , Pneumopatias Obstrutivas/complicações , Vacinação , Administração Intranasal , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/análise , Citocinas/biossíntese , Método Duplo-Cego , Humanos , Imunoglobulina A/análise , Vírus da Influenza A/isolamento & purificação , Vacinas contra Influenza/efeitos adversos , Influenza Humana/imunologia , Influenza Humana/fisiopatologia , Injeções Intramusculares , Pneumopatias Obstrutivas/imunologia , Pneumopatias Obstrutivas/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Testes de Função Respiratória , Segurança , Resultado do Tratamento , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/efeitos adversosRESUMO
Induction of local antibody responses to influenza A virus hemagglutinin by coadministration of two vaccines was investigated. Fifty elderly nursing home residents received inactivated trivalent influenza virus vaccine intramuscularly and simultaneously were randomized to receive either bivalent live attenuated influenza A virus vaccine or saline placebo intranasally in a blinded fashion. More significant increases in anti-H1 and -H3 IgA antibodies were detectable in nasal wash specimens of subjects who received live attenuated virus vaccine than in those who received intranasal placebo. The increased anti-hemagglutinin IgA antibody response was of longer duration in recipients of live attenuated vaccine. The change in antibody titers after vaccination was positively correlated with total blood lymphocyte counts measured before vaccination in both vaccinee groups (P < .05). There was a possible advantage of administering live attenuated with inactivated virus vaccines because of enhanced local antibody responses.
Assuntos
Anticorpos Antivirais/biossíntese , Vírus da Influenza A/imunologia , Vacinas contra Influenza/administração & dosagem , Mucosa Nasal/imunologia , Idoso , Método Duplo-Cego , Feminino , Glicoproteínas de Hemaglutininação de Vírus da Influenza , Hemaglutininas Virais/imunologia , Instituição de Longa Permanência para Idosos , Humanos , Imunoglobulina A/análise , Imunoglobulina A Secretora/análise , Vírus da Influenza A/isolamento & purificação , Contagem de Linfócitos , Masculino , Líquido da Lavagem Nasal/imunologia , Mucosa Nasal/virologia , Casas de Saúde , Vacinação , Vacinas Atenuadas/administração & dosagem , Vacinas de Produtos Inativados/administração & dosagem , Proteínas do Envelope Viral/imunologia , Eliminação de Partículas ViraisRESUMO
The possible enhancement of anti-influenza A virus memory cytotoxic T cell (CTL) responses to inactivated influenza virus vaccine by coadministration of intranasal live attenuated influenza A virus vaccine was investigated. Fifty elderly nursing home residents received inactivated trivalent influenza virus vaccine intramuscularly and simultaneously were randomly assigned to receive either bivalent live attenuated influenza A virus vaccine or saline placebo intranasally in a blinded fashion. A larger proportion of volunteers who received live attenuated virus vaccine than of those who received placebo experienced a postvaccination rise in anti-influenza A virus CTL activity (15 of 23 vs. 8 of 24; P < .05). Anti-influenza A virus cytotoxicity was primarily mediated by CD8+ T cells and was influenza A virus-specific and HLA-restricted. There was a possible advantage of administering live attenuated with inactivated virus vaccine because of enhanced memory anti-influenza A virus CTL activity.
