How Can Vaccines Against Influenza and Other Viral Diseases Be Made More Effective?

Peter L Nara,Wilfred Ndifon,A Ray Chaudhuri,Jessie D Trujillo,Simon A Levin,George Lin,Michael W Cho,Gregory J Tobin,Ned S Wingreen

doi:10.1371/journal.pbio.1000571

Abstract

A large fraction of the world's most widespread and problematic pathogens, such as the influenza virus, seem to persist in nature by evading host immune responses by inducing immunity to genetically and phenotypically plastic epitopes (aka antigenic variation). The more recent re-emergence of pandemic influenza A/H1N1 and avian H5N1 viruses has called attention to the urgent need for more effective influenza vaccines. Developing such vaccines will require more than just moving from an egg-based to a tissue-culture–based manufacturing process. It will also require a new conceptual understanding of pathogen–host interactions, as well as new approaches and technologies to circumvent immune evasion by pathogens capable of more genetic variation. Here, we discuss these challenges, focusing on some potentially fruitful directions for future research.

Highlights

Two important challenges for current influenza research are to explain the mechanisms involved in creating and maintaining the highly restricted diversity of epidemic strains and to develop more broadly efficacious vaccines capable of protecting against future epidemics
We argue here that the observed strain-to-strain, year-to-year variation is in part a consequence of another important contributor to the rapid emergence of immune-evading variants, namely the propensity of the host immune system to develop antibodies to immunodominant epitopes located in variable regions of the viral envelope protein(s) (e.g., HA and NA)
The interesting and paradoxical outcome of this immunodominant epitope–antibody interaction is that it appears to lead to effective, highly strain-specific antibodies while at the same time sterically interfering with the generation of more broadly reactive antibodies [1,2,3,4]

Summary

Introduction

Two important challenges for current influenza research are to explain the mechanisms involved in creating and maintaining the highly restricted diversity of epidemic strains and to develop more broadly efficacious vaccines capable of protecting against future epidemics. Continued epidemiological importance of the influenza virus derives in part from its ability to generate new annual strains capable of evading host immunity.

Results

Conclusion