The latest article in our Current Concepts series, “Influenza Vaccines for the Future,” comes from Drs. Linda C. Lambert and Anthony S. Fauci of the National Institute of Allergy and Infectious Diseases in Bethesda.
Each year, seasonal epidemics of influenza cause serious illness and death throughout the world. In the United States, the annual burden of disease is estimated to be 25 to 50 million cases of influenza, resulting in an average of 225,000 hospitalizations.
• Why are new vaccine options against influenza needed?
Although both inactivated vaccines and the live attenuated vaccine are effective in preventing influenza and its associated complications, the protection they confer varies widely, depending on the antigenic match between the viruses in the vaccine and those that are circulating during a given influenza season and on the recipient’s age and health status. More effective vaccination options are needed, especially for persons who do not have a good response to vaccination, including the elderly and those with chronic underlying disease.
• What are the likely characteristics of the next generation of influenza vaccines?
Although cell-based influenza vaccines and vaccines containing adjuvants are likely to facilitate the production of influenza vaccines within several years, recombinant DNA techniques are enabling new production strategies by allowing vaccine candidates to be generated as soon as the genetic sequence of the influenza virus HA is known; this approach would eliminate the need to handle pathogenic viruses or to adapt viruses to grow in eggs or cells.
Table 1. Current and New Approaches to Influenza-Vaccine Production.
Morning Report Questions
Q: What is the role of newer adjuvants to help promote antigenicity of vaccines?
A: Clinical trials have shown that oil-in-water adjuvants are needed to stimulate high levels of antibodies against influenza viruses that have novel HAs (e.g., H5N1 viruses), and these adjuvants may be critically important in future vaccination programs. Purified bacterial outer-membrane proteins, toll-like receptors, and a variety of toll-like-receptor agonists (bacterial carbohydrates, lipids, proteins, and nucleic acids) have shown promise as next-generation adjuvants for influenza vaccines.
Q: What novel live attenuated viruses are in development?
A: Efforts also are under way to develop live influenza vaccines based on the influenza NS1 protein, a nonstructural, multifunctional protein involved in viral replication and inhibition of the host’s innate immune responses. Preclinical studies have shown that infection with viruses containing an altered or deleted NS1 protein blocks viral replication and stimulates both humoral and cellular immune responses. Early clinical data have shown that an intranasal NS1 vaccine is well tolerated and generates neutralizing HA antibodies.