Vaccines for Pandemic Influenza

Recent years have seen unprecedented outbreaks of avian influenza A viruses. In particular, highly pathogenic H5N1 viruses have not only resulted in widespread outbreaks in domestic poultry, but have been transmitted to humans, resulting in numerous fatalities. The rapid expansion in their geographic distribution and the possibility that these viruses could acquire the ability to spread from person to person raises the risk that such a virus could cause a global pandemic with high morbidity and mortality. An effective influenza vaccine represents the best approach to prevent and control such an emerging pandemic. However, current influenza vaccines are directed at existing seasonal influenza viruses, which have little or no antigenic relationship to the highly pathogenic H5N1 strains. Concerns about pandemic preparedness have greatly stimulated research activities to develop eff- tive vaccines for pandemic influenza viruses, and to overcome the limitations inh- ent in current approaches to vaccine production and distribution. These limitations include the use of embryonated chicken eggs as the substrate for vaccine prod- tion, which is time-consuming and could involve potential biohazards in growth of new virus strains. Other limitations include the requirement that the current inac- vated influenza vaccines be administered using needles and syringes, requiring trained personnel, which could be a bottleneck when attempting to vaccinate large populations in mass campaigns. In addition, the current inactivated vaccines that are delivered by injection elicit limited protective immunity in the upper respiratory tract where the infection process is initiated.

Pandemic Influenza Overview.- Pandemic Influenza as a Current Threat.- Antigenic Cross-Reactivity Among H5N1 Viruses.- Current Approaches for Human and Avian Vaccine Production.- Seasonal Influenza Vaccines.- Generation and Characterization of Candidate Vaccine Viruses for Prepandemic Influenza Vaccines.- Live Attenuated Vaccines for Pandemic Influenza.- Influenza Vaccines for Avian Species.- Development and Application of Avian Influenza Vaccines in China.- Novel Vaccine Approaches.- Designing Vaccines for Pandemic Influenza.- Attenuated Influenza Virus Vaccines with Modified NS1 Proteins.- DNA Vaccines Against Influenza Viruses.- Recombinant Proteins Produced in Insect Cells.- Influenza Neuraminidase as a Vaccine Antigen.- Recombinant Vectors as Influenza Vaccines.- Influenza Virus-Like Particles as Pandemic Vaccines.- Pandemic Influenza Vaccines.- Adjuvants for Pandemic Influenza Vaccines.- Novel Approaches for Vaccine Delivery.- Transcutaneous Immunization with Influenza Vaccines.- Microneedle-Based Vaccines.- Vaccine Evaluation, Production and Distribution.- Animal Models for Evaluation of Influenza Vaccines.- Immunosenescence and Influenza Vaccine Efficacy.- Vaccines for Pandemic Influenza: Summary of Recent Clinical Trials.- Considerations for Licensure of Influenza Vaccines with Pandemic and Prepandemic Indications.- Strategies for Broad Global Access to Pandemic Influenza Vaccines.- Prioritization of Pandemic Influenza Vaccine: Rationale and Strategy for Decision Making.