RESUMO
Influenza DNA vaccines have been widely studied in experimental animal models and protection documented after lethal viral challenge. In this study, we have investigated the humoral response after a non-lethal viral challenge of mice vaccinated with plasmids encoding the influenza haemagglutinin (HA) or nucleoprotein (NP) genes. BALB/c mice were immunized intramuscularly with three doses (100 microg) of HA, NP or backbone plasmid at 3-week intervals, or alternatively infected intranasally, before being challenged with homologous virus 13 weeks later. Mice were then sacrificed at weekly intervals and the antibody-secreting cell response was examined systemically (spleen and bone marrow) and in the respiratory tract (nasal associated lymphoid tissue (NALT) and lungs). Sera were collected after each dose of vaccine and at sacrifice and analyzed by ELISA, haemagglutination inhibition and virus neutralization assays. We found that previous viral infection apparently elicits sterilizing immunity. Vaccination with HA or NP DNA significantly reduced viral replication in the nasal cavity after viral challenge, however, increases in serum antibody titres were observed after challenge. Prior to challenge, specific antibody-secreting cells were observed in the systemic compartment after HA or NP DNA vaccination but were also found in the NALT after viral challenge. In conclusion, intramuscular DNA vaccination resulted in immunological memory in the systemic compartment, which was rapidly reactivated upon viral challenge.
Assuntos
Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Vacinas contra Influenza/farmacologia , Nucleoproteínas/imunologia , Orthomyxoviridae/imunologia , Orthomyxoviridae/fisiologia , Vacinas de DNA/farmacologia , Animais , Anticorpos Antivirais/sangue , Células Produtoras de Anticorpos/imunologia , Antígenos Virais/genética , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Imunoglobulina G/sangue , Imunoglobulina G/classificação , Memória Imunológica , Vacinas contra Influenza/genética , Tecido Linfoide/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Testes de Neutralização , Nucleoproteínas/genética , Orthomyxoviridae/genética , Orthomyxoviridae/patogenicidade , Plasmídeos/genética , Vacinas de DNA/genética , Replicação Viral/imunologiaRESUMO
Zanamivir is licensed for influenza treatment, but may also play a role in prophylaxis either alone or in combination with vaccine in epidemic periods. We conducted a double blind placebo controlled trial to investigate the effect of zanamivir treatment on the humoral immune response to influenza vaccine. Forty young healthy volunteers were vaccinated with licensed trivalent influenza vaccine and received 20 mg zanamivir (24 subjects) or placebo (16 subjects) daily for a period of 14 days. No significant differences were observed in the magnitude or the time course of the antibody response to the influenza H3N2 and B strains between the two groups, in contrast the placebo group responded with higher antibody titres to the H1N1. Our results suggest that during an influenza epidemic, volunteers would only need to continue zanamivir treatment for the initial 12 days after vaccination whilst the vaccine induced protective antibody response developed.
