Comparison of influenza virus replication fidelity in vitro using selection pressure with monoclonal antibodies

Abstract

The replication fidelity of reassortant A/Fujian/411/02(H3N2)-like influenza viruses was assessed by in vitro detection of escape mutants developing under selective pressure from monoclonal antibodies. The results showed A/Wyoming/3/03(H3N2) possessed lower fidelity relative to the A/California/7/04(H3N2) and A/Wisconsin/57/05(H3N2) viruses through the emergence of mutant viruses carrying H156Q hemagglutinin mutation which allows antibody escape. Using the neutralization assay to compare the fidelity of reassortant pandemic A/California/7/09(H1N1) viruses, the pandemic virus was shown to possess relative higher fidelity compared to A/Wyoming/3/03. This higher fidelity may contribute to the lack of major antigenic changes in the pandemic virus since the emergence in 2009.

Construction and Immunogenicity of a Novel Multivalent Vaccine Prototype Based on Conserved Influenza Virus Antigens

“…Continuous antibody-mediated immune pressure and the lack of a proof-reading function for RNA polymerase errors result in accumulation of point mutations in the hemagglutinin (HA) and neuraminidase genes and in constant emergence of mutant variants affecting immune recognition. This process, characteristic to both influenza A and B viruses, is known as antigenic drift and it has the potential to cause local outbreaks and seasonal epidemics [7][8][9][10]. Moreover, sporadic reassortment of segmented influenza A virus genomes in a double-infected host cell can result in an antigenic shift, which can lead to a global pandemic by producing an unpredicted virus strain to which the immunologically naive human population is particularly susceptible.…”

Recalling the Future: Immunological Memory Toward Unpredictable Influenza Viruses

“…The influenza virus RNA polymerase lacks proof-reading function, with the consequence that there is a constant emergence of mutants (affecting viral fitness and/or immune recognition) carrying substitutions that arise randomly across the genome. Antibody-mediated immune pressure drives the selection of viruses expressing variant HAs and NAs (13, 14) that, if their “fitness” is not unduly compromised, have the potential in nature to cause the process that has long been called antigenic drift (15, 16). Clearly, for a drifted strain to emerge as a clinical problem, its HA must be sufficiently changed to escape neutralization by pre-existing antibodies induced broadly in human populations by past infections and/or vaccinations.…”