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Proc Natl Acad Sci U S A. 2014 Sep 9;111(36):13133-8. doi: 10.1073/pnas.1414070111. Epub 2014 Aug 25.

Induction of broadly cross-reactive antibody responses to the influenza HA stem region following H5N1 vaccination in humans.

Author information

1
Emory Vaccine Center, and Department of Microbiology and Immunology.
2
Department of Microbiology.
3
Emory Vaccine Center, and Department of Pediatrics.
4
Emory Transplant Center, Emory University School of Medicine, Atlanta, GA 30322;
5
Division of Infectious Diseases, Department of Medicine.
6
Department of Pediatrics.
7
Department of Medicine, Section of Rheumatology, Committee on Immunology, The Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, IL 60637.
8
Department of Microbiology, Department of Medicine, and Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029; and.
9
Division of Infectious Diseases, Department of Medicine, Hope Clinic of the Emory Vaccine Center.
10
Emory Transplant Center, Emory University School of Medicine, Atlanta, GA 30322; Division of Infectious Diseases, Department of Medicine, Hope Clinic of the Emory Vaccine Center.
11
Department of Microbiology, Department of Medicine, and.
12
Emory Vaccine Center, and Department of Microbiology and Immunology, rahmed@emory.edu.

Abstract

The emergence of pandemic influenza viruses poses a major public health threat. Therefore, there is a need for a vaccine that can induce broadly cross-reactive antibodies that protect against seasonal as well as pandemic influenza strains. Human broadly neutralizing antibodies directed against highly conserved epitopes in the stem region of influenza virus HA have been recently characterized. However, it remains unknown what the baseline levels are of antibodies and memory B cells that are directed against these conserved epitopes. More importantly, it is also not known to what extent anti-HA stem B-cell responses get boosted in humans after seasonal influenza vaccination. In this study, we have addressed these two outstanding questions. Our data show that: (i) antibodies and memory B cells directed against the conserved HA stem region are prevalent in humans, but their levels are much lower than B-cell responses directed to variable epitopes in the HA head; (ii) current seasonal influenza vaccines are efficient in inducing B-cell responses to the variable HA head region but they fail to boost responses to the conserved HA stem region; and (iii) in striking contrast, immunization of humans with the avian influenza virus H5N1 induced broadly cross-reactive HA stem-specific antibodies. Taken together, our findings provide a potential vaccination strategy where heterologous influenza immunization could be used for increasing the levels of broadly neutralizing antibodies and for priming the human population to respond quickly to emerging pandemic influenza threats.

KEYWORDS:

breadth; immunoglobulin; neutralization; stalk

PMID:
25157133
PMCID:
PMC4246941
DOI:
10.1073/pnas.1414070111
[Indexed for MEDLINE]
Free PMC Article

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