Antibody Focusing to Conserved Sites of Vulnerability: The Immunological Pathways for ‘Universal’ Influenza Vaccines
Open Access
- 5 February 2021
- Vol. 9 (2), 125
- https://doi.org/10.3390/vaccines9020125
Abstract
Influenza virus remains a serious public health burden due to ongoing viral evolution. Vaccination remains the best measure of prophylaxis, yet current seasonal vaccines elicit strain-specific neutralizing responses that favor the hypervariable epitopes on the virus. This necessitates yearly reformulations of seasonal vaccines, which can be limited in efficacy and also shortchange pandemic preparedness. Universal vaccine development aims to overcome these deficits by redirecting antibody responses to functionally conserved sites of viral vulnerability to enable broad coverage. However, this is challenging as such antibodies are largely immunologically silent, both following vaccination and infection. Defining and then overcoming the immunological basis for such subdominant or ‘immuno-recessive’ antibody targeting has thus become an important aspect of universal vaccine development. This, coupled with structure-guided immunogen design, has led to proof-of-concept that it is possible to rationally refocus humoral immunity upon normally ‘unseen’ broadly neutralizing antibody targets on influenza virus.Keywords
Funding Information
- National Institutes of Health (R01AI137057, DP2DA042422, R01AI124378, R01AI153098, R01AI155447)
This publication has 219 references indexed in Scilit:
- Discordant antigenic drift of neuraminidase and hemagglutinin in H1N1 and H3N2 influenza virusesProceedings of the National Academy of Sciences of the United States of America, 2011
- Viva la revolución: rethinking influenza A virus antigenic driftCurrent Opinion in Virology, 2011
- Broadly neutralizing human antibody that recognizes the receptor-binding pocket of influenza virus hemagglutininProceedings of the National Academy of Sciences of the United States of America, 2011
- A New Clustering of Antibody CDR Loop ConformationsJournal of Molecular Biology, 2011
- Structure and function of immunoglobulinsJournal of Allergy and Clinical Immunology, 2010
- Structural and functional bases for broad-spectrum neutralization of avian and human influenza A virusesNature Structural & Molecular Biology, 2009
- Combinatorial antibody libraries from survivors of the Turkish H5N1 avian influenza outbreak reveal virus neutralization strategiesProceedings of the National Academy of Sciences of the United States of America, 2008
- Structure and mechanism of the M2 proton channel of influenza A virusNature, 2008
- Structure of the haemagglutinin membrane glycoprotein of influenza virus at 3 Å resolutionNature, 1981
- The role of serum haemagglutination-inhibiting antibody in protection against challenge infection with influenza A2 and B virusesEpidemiology and Infection, 1972