Is It Possible to Develop a "Universal" Influenza Virus Vaccine?

[tetano]

Cold Spring Harb Perspect Biol. 2017 Jun 29. pii: a028852. doi: 10.1101/cshperspect.a028852. [Epub ahead of print]
Is It Possible to Develop a "Universal" Influenza Virus Vaccine? Outflanking Antibody Immunodominance on the Road to Universal Influenza Vaccination.

Angeletti D¹, Yewdell JW¹.
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Abstract

Influenza remains a major human pathogen despite seasonal vaccination. At long last, there is energy and resources to develop influenza vaccines that provide more predictable and durable protection. Vaccines based on inducing antibodies to the conserved stem of the viral hemagglutinin (HA) have emerged as leading candidates for broadening population immunity and ultimately limiting antigenic drift. Here, we discuss the knowns and unknowns of HA-specific B-cell and antibody responses. In particular, we focus on how immunodominance sculpts antibody responses and drives antigenic drift. We propose a number of strategies to overcome immunodominance and improve the breadth and efficacy of antibody responses.
Copyright ? 2017 Cold Spring Harbor Laboratory Press; all rights reserved.


PMID: 28663210 DOI: 10.1101/cshperspect.a028852

[tetano]

Cold Spring Harb Perspect Biol. 2017 Jun 29. pii: a028845. doi: 10.1101/cshperspect.a028845. [Epub ahead of print]
Is It Possible to Develop a "Universal" Influenza Virus Vaccine? Toward a Universal Influenza Virus Vaccine: Potential Target Antigens and Critical Aspects for Vaccine Development.

Krammer F¹, Garc?a-Sastre A^1,2,3, Palese P^1,3.
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Abstract

Influenza viruses cause seasonal epidemics as well as pandemics and are a significant concern for human health. Current influenza virus vaccines show efficacy when they are antigenically well matched to circulating strains. Seasonal influenza viruses undergo antigenic drift at a high rate and, therefore, current vaccines have to be reformulated and readministered on an annual basis. Mismatches between vaccine strains and circulating strains frequently occur, significantly decreasing vaccine efficacy. In addition, current seasonal influenza virus vaccines have limited efficacy against newly emerging pandemic viruses. A universal influenza virus vaccine that induces long-term protection against all influenza virus strains would abolish the need for annual readministration of seasonal influenza virus vaccines and would significantly enhance our pandemic preparedness. Here we discuss the characteristics of universal influenza virus vaccines, their potential target antigens, and critical aspects to consider on the path to successfully developing such vaccines.
Copyright ? 2017 Cold Spring Harbor Laboratory Press; all rights reserved.


PMID: 28663209 DOI: 10.1101/cshperspect.a028845

[tetano]

Cold Spring Harb Perspect Biol. 2017 Jun 29. pii: a029496. doi: 10.1101/cshperspect.a029496. [Epub ahead of print]
Is It Possible to Develop a "Universal" Influenza Virus Vaccine? Potential for a Universal Influenza Vaccine.

Crowe JE Jr¹.
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Abstract

Development of optimal vaccines for influenza is challenging, in part as a result of the high antigenic variability in field strains associated with genetic shift from reassortment and genetic drift from point mutations. Discovery of conserved antigenic sites on the hemagglutinin (HA) protein for neutralizing antibodies suggested the possibility that influenza vaccines could be developed that induce focused antibody responses to the conserved neutralizing determinants, especially the HA stem region. Recent studies have focused on the antigenicity and immunogenicity of such domains, using monoclonal antibodies and candidate-engineered HA stem-based vaccines. Much progress has been made, but we still do not fully understand the biology of the immune response to this unique antigenic region.
Copyright ? 2017 Cold Spring Harbor Laboratory Press; all rights reserved.


PMID: 28663208 DOI: 10.1101/cshperspect.a029496

[tetano]

Cold Spring Harb Perspect Biol. 2017 Jun 29. pii: a029413. doi: 10.1101/cshperspect.a029413. [Epub ahead of print]
Is It Possible to Develop a "Universal" Influenza Virus Vaccine? Immunogenetic Considerations Underlying B-Cell Biology in the Development of a Pan-Subtype Influenza A Vaccine Targeting the Hemagglutinin Stem.

Andrews SF¹, Graham BS¹, Mascola JR¹, McDermott AB¹.
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Abstract

Current influenza vaccines preferentially generate B-cell responses to the variable hemagglutinin (HA) head. Focusing vaccine-induced antibody responses on epitopes in the conserved HA stem may provide better protection against future drifted and pandemic strains. Understanding the basis for the dominant HA head and subdominant HA stem-specific responses at the level of B-cell activation and differentiation will be critical for designing vaccines that induce sustained stem-specific responses. Identifying antibody lineages with broad neutralizing activity against influenza A viruses and defining the structural mode of recognition for germline precursors of those antibodies will also guide future immunogen design.
Copyright ? 2017 Cold Spring Harbor Laboratory Press; all rights reserved.


PMID: 28663207 DOI: 10.1101/cshperspect.a029413