Prophylaxis and treatment of influenza virus infection

Influenza virus infections remain an important cause of morbidity and morta lity. Furthermore, a recurrence of pandemic influenza remains a real possib ility. There are now effective ways to both prevent and treat influenza, Pr evention of infection is most effectively accomplished by vaccination. Vacc ination with the inactivated, intramuscular influenza vaccine has been clea rly demonstrated to reduce serious morbidity and mortality associated with influenza infection, especially in groups of patients at high risk (e.g. th e elderly). However, the inactivated, intramuscular vaccine does not strong ly induce cell-mediated or mucosal immune responses, and protection induced by the vaccine is highly strain specific. Live, attenuated influenza vacci nes administered intranasally have been studied in clinical trials and show n to elicit stronger mucosal and cell-mediated immune responses. Live, atte nuated vaccines appear to be more effective for inducing protective immunit y in children or the elderly than inactivated, intramuscular vaccines. Addi tionally. novel vaccine methodologies employing conserved components of inf luenza virus or viral DNA are being developed. Preclinical studies suggest that these approaches may lead to methods of vaccination that could induce immunity against diverse strains or subtypes of influenza. Because of the limitations of vaccination, antiviral therapy continues to p lay an important role in the control of influenza. Two major classes of ant ivirals have demonstrated ability to prevent or treat influenza in clinical trials: the adamantanes and the neuraminidase inhibitors. The adamantanes (amantadine and rimantadine) have been in use for many years. They inhibit viral uncoating by blocking the proton channel activity of the influenza A viral M2 protein. Limitations of the adamantanes include lack of activity a gainst influenza B, toxicity (especially in the elderly), and the rapid dev elopment of resistance. The neuraminidase inhibitors were designed to inter fere with the conserved sialic acid binding site of the viral neuraminidase and act against both influenza A and B with a high degree of specificity w hen administered by the oral (oseltamivir) or inhaled (zanamivir) route. Th e neuraminidase inhibitors have relatively low toxicity, and viral resistan ce to these inhibitors appears to be uncommon. Additional novel antivirals that target other phases of the life cycle of influenza are in preclinical development. For example, recombinant collectins inhibit replication of inf luenza by binding to the viral haemagglutinin as well as altering phagocyte responses to the virus. Recombinant techniques have been used for generati on of antiviral proteins (e.g. modified collectins) or oligonucleotides. Greater understanding of the biology of influenza viruses has already resul ted in significant advances in the management of this important pathogen. F urther advances in vaccination and antiviral therapy of influenza should re main a high priority.