tetano
Editor, Senior Moderator
Proc Natl Acad Sci U S A. 2014 Aug 25. pii: 201414070. [Epub ahead of print]
Induction of broadly cross-reactive antibody responses to the influenza HA stem region following H5N1 vaccination in humans.
Ellebedy AH1, Krammer F2, Li GM1, Miller MS2, Chiu C1, Wrammert J3, Chang CY1, Davis CW1, McCausland M1, Elbein R4, Edupuganti S5, Spearman P6, Andrews SF7, Wilson PC7, Garc?a-Sastre A8, Mulligan MJ9, Mehta AK10, Palese P11, Ahmed R12.
Author information
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
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25157133
Induction of broadly cross-reactive antibody responses to the influenza HA stem region following H5N1 vaccination in humans.
Ellebedy AH1, Krammer F2, Li GM1, Miller MS2, Chiu C1, Wrammert J3, Chang CY1, Davis CW1, McCausland M1, Elbein R4, Edupuganti S5, Spearman P6, Andrews SF7, Wilson PC7, Garc?a-Sastre A8, Mulligan MJ9, Mehta AK10, Palese P11, Ahmed R12.
Author information
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
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25157133