Second WHO meeting on the development of influenza vaccines that induce broad spectrum and long-lasting immune responses, 6-7 December 2005, WHO HQ Geneva
Summary, Opening and Keynote Presentations
In 2004, WHO established a research project to promote the development of a new generation of influenza vaccines that induce broad spectrum and long-lasting immune responses and provide protection against divergent influenza viruses. New vaccines should overcome problem with the current vaccination strategy, based on annual intervention, be affordable in developing countries and contribute to epidemic and potential pandemic response.
On 6-7 December 2005 the World Health Organization held a meeting on the “Development of influenza vaccines that induce broad spectrum and long-lasting immune responses” at its headquarters in Geneva, Switzerland. The meeting was a follow-up to a previous meeting on the same subject conducted 26-27th February 2004 and its objectives were:
- To review the current status of research in the area of influenza vaccines, focusing on strategies to induce broad spectrum and long-lasting immune responses and to provide cross-protection against different influenza viruses and;
- To establish a research agenda for the development of influenza vaccine with broad-spectrum and long-lasting immune responses.
The evidence for naturally occurring heterosubtypic influenza immunity in humans was reviewed. It was concluded that while heterosubtypic influenza immunity induced by natural infection is weak in humans there is evidence that an effective memory adaptive immune response follows vaccination and may in fact modulate the severity of influenza infection.
A review of the data on live attenuated, cold-adapted (CA) influenza vaccines demonstrated a history of safety, high level of protection including against drift variants, evidence of herd immunity through the vaccination of children and the potential for early, possibly interferon-based, protection shortly after vaccine administration. There is some evidence of greater protection than protection induced by inactivated vaccines; however, head-to-head comparisons are limited.
The influenza A M2 protein and epitopes of its ecto-domain have been extensively studied as candidate broad-spectrum vaccines. Cross-protection induced by M2 protein was shown in many studies in animals. Mode of action appears to be NK cell-dependent via antibody-dependent cellular cytotoxicity rather than virus neutralization. A number of approaches have been found to enhance the antibody response to the M2 ectodomain including fusion with various proteins, coupling with carrier proteins and delivery in a viral vector or in virus-like particles.
Other approaches that have demonstrated promise for broad spectrum influenza A protection in animal models include conjugated viral antigens and DNA vaccines.
Research agenda for development of cross-protective vaccine was revised and specific recommendations for WHO activity were formulated.