tetano
Editor, Senior Moderator
J Virol. 2015 Nov 4. pii: JVI.02757-15. [Epub ahead of print]
[h=1]Correlation between virus replication and antibody responses in macaques following infection with pandemic influenza A virus.[/h] Koopman G[SUP]1[/SUP], Mooij P[SUP]2[/SUP], Dekking L[SUP]3[/SUP], Mortier D[SUP]1[/SUP], Nieuwenhuis I[SUP]1[/SUP], van Heteren M[SUP]1[/SUP], Kuipers H[SUP]3[/SUP], Remarque EJ[SUP]1[/SUP], Rado?ević K[SUP]3[/SUP], Bogers WM[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Influenza virus infection of non-human primates is a well-established animal model for studying pathogenesis and for evaluating prophylactic and therapeutic intervention strategies. However, usually a standard dose is used for the infection and there is no information on relation between challenge dose and virus replication or the induction of immune responses. Such information is also very scarce in humans and largely confined to evaluation of attenuated virus strains. Here we have compared the effect of a commonly used dose (4 x 10[SUP]6[/SUP] TCID[SUB]50[/SUB]) versus a hundred fold higher dose, given by intra-bronchial installation, in two groups of 6 cynomolgus macaques. Animals infected with the high virus dose showed more fever and had higher peak levels of IFNγ in the blood. However, virus replication in the trachea was not significantly different between the groups, although in 2 out of 6 animals from the high dose group it was present at higher levels and for a longer duration. The virus specific antibody response was not significantly different between the groups. However, antibody ELISA, virus neutralization and hemaglutination inhibition antibody titers correlated with cumulative virus production in the trachea. In conclusion, using influenza virus infection in cynomolgus macaques as a model, we demonstrated a relationship between level of virus production upon infection and induction of functional antibody responses against the virus.
[h=4]IMPORTANCE:[/h] There is only very limited information on the effect of virus inoculation dose on the level of virus production and the induction of adaptive immune responses in humans or non-human primates. We showed only a marginal and variable effect of virus dose on virus production in the trachea, but a significant effect on body temperature. The induction of functional antibody responses, including virus neutralization titer, hemagglutination inhibition titer and antibody dependent cell mediated cytotoxicity, correlated with the level of virus replication measured in the trachea. The study reveals a relationship between virus production and functional antibody formation, which could be relevant in defining appropriate criteria for new influenza virus vaccine candidates.
Copyright ? 2015, American Society for Microbiology. All Rights Reserved.
PMID: 26537681 [PubMed - as supplied by publisher]
[h=1]Correlation between virus replication and antibody responses in macaques following infection with pandemic influenza A virus.[/h] Koopman G[SUP]1[/SUP], Mooij P[SUP]2[/SUP], Dekking L[SUP]3[/SUP], Mortier D[SUP]1[/SUP], Nieuwenhuis I[SUP]1[/SUP], van Heteren M[SUP]1[/SUP], Kuipers H[SUP]3[/SUP], Remarque EJ[SUP]1[/SUP], Rado?ević K[SUP]3[/SUP], Bogers WM[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Influenza virus infection of non-human primates is a well-established animal model for studying pathogenesis and for evaluating prophylactic and therapeutic intervention strategies. However, usually a standard dose is used for the infection and there is no information on relation between challenge dose and virus replication or the induction of immune responses. Such information is also very scarce in humans and largely confined to evaluation of attenuated virus strains. Here we have compared the effect of a commonly used dose (4 x 10[SUP]6[/SUP] TCID[SUB]50[/SUB]) versus a hundred fold higher dose, given by intra-bronchial installation, in two groups of 6 cynomolgus macaques. Animals infected with the high virus dose showed more fever and had higher peak levels of IFNγ in the blood. However, virus replication in the trachea was not significantly different between the groups, although in 2 out of 6 animals from the high dose group it was present at higher levels and for a longer duration. The virus specific antibody response was not significantly different between the groups. However, antibody ELISA, virus neutralization and hemaglutination inhibition antibody titers correlated with cumulative virus production in the trachea. In conclusion, using influenza virus infection in cynomolgus macaques as a model, we demonstrated a relationship between level of virus production upon infection and induction of functional antibody responses against the virus.
[h=4]IMPORTANCE:[/h] There is only very limited information on the effect of virus inoculation dose on the level of virus production and the induction of adaptive immune responses in humans or non-human primates. We showed only a marginal and variable effect of virus dose on virus production in the trachea, but a significant effect on body temperature. The induction of functional antibody responses, including virus neutralization titer, hemagglutination inhibition titer and antibody dependent cell mediated cytotoxicity, correlated with the level of virus replication measured in the trachea. The study reveals a relationship between virus production and functional antibody formation, which could be relevant in defining appropriate criteria for new influenza virus vaccine candidates.
Copyright ? 2015, American Society for Microbiology. All Rights Reserved.
PMID: 26537681 [PubMed - as supplied by publisher]