Influenza: Brief Comments on the Recent 2009 Influenza A(H1N1) Epidemic and Observations on Vaccine

Sporadic outbreaks of highly virulent avian H5N1 influenza and the recent outbreak of a pandemic A(H1N1) virus have heightened concerns about the eventual emergence of a particularly deadly pandemic virus. Influenza A virus represents one of the most prominent viral pathogens of modern times. Infection with this microbe results in an estimated 36,000 deaths¹ and over 200,000 hospitalizations² in the United States annually, with a projected total economic burden in excess of 80 billion US dollars per year.³ According to the Centers for Disease Control and Prevention, the incidence of influenza virus infection in the US population may reach 20% during a typical flu season; however, this figure can increase substantially during periods of pandemic influenza. Although influenza is typically a self-limiting disease, serious complications can occur, including primary viral pneumonia, secondary bacterial pneumonia, myositis, and neurologic syndromes. The risk of mortality and disease complications is elevated for certain populations, including the young, old, immunosuppressed, and immunocompromised. During the most recent pandemic, infection/disease was witnessed in unique populations, such as pregnant women and children, with substantial mortality observed. Elderly individuals were not as predisposed, reflecting previous serologic evidence of prior exposure to similar influenza virus strains. The epidemic demonstrated differences in treatment efficacy for drugs; potential utilities of intensive support, including alternate ventilatory modes such as extracorporeal membrane oxygenation; and difficulties in administering and allocating resources. Interactions among physicians, health-care delivery systems, and administrations were stressed. The ability of influenza A virus to infect millions of people each year speaks to the resilient nature of this pathogen and to the necessity for developing improved methods of disease prevention and treatment.

Although commercial influenza vaccines have been available since the mid-1900s, a number of key challenges continue to limit the efficacy of these vaccines. The rapid mutation rate of immunodominant glycoproteins on the virus surface necessitates annual revision of the vaccine and requires a broad network of laboratories to cooperatively perform surveillance on circulating influenza virus strains throughout the year. Importantly, current strain-specific vaccines are only 30% to 50% effective in preventing hospitalization and pneumonia in the elderly and are about 70% effective in preventing illness in healthy adults. Most recently (late 2010), several groups have observed disturbing trends of mistrust of vaccine formulations (individual components), which have resulted in refusal of vaccination by health-care persons of all types, including physicians and nurses.

Despite the extensive variability in strains of seasonal influenza, some research investigations have indicated the potential for developing universally protective immune responses against influenza viruses. Over the past decade, an array of conserved influenza virus epitopes have been identified, and the ability of both cell-mediated immune components and humoral immune components to elicit crossprotective immunity to heterologous influenza A viruses have been documented. Moreover, the improvement of influenza vaccine immunogenicity via inclusion of molecular adjuvants and modification of vaccine modality has been widely reported but rarely within the context of a universal influenza vaccine. Development of a maximally efficacious vaccine in primates may require alternative approaches, such as a combinatorial formulation containing both immunomodulatory components and conserved influenza antigens.

Further research is necessary to refine approaches to management of influenza, both in prevention and treatment.

1. Molinari NA, Ortega-Sanchez IR, Messonnier ML, et al. The annual impact of seasonal influenza in the US: measuring disease burden and costs. Vaccine. 2007;25(27):5086-5096.
2. Thompson W, Weintraub E, Dhankhar P, et al. Estimates of US influenza- associated deaths made using four different methods. Influenza Other Respi Viruses. 2009;3(1):37-49.
3. Thompson WW, Shay DK, Weintraub E, et al. Influenza-associated hospitalizations in the United States. JAMA. 2004;292(11):1333-1340.

Dr Joel F. Aldrich; and
Dr Richard E. Winn, FCCP,
NetWork Steering Committee Member