BACKGROUND: Infection with pandemic H1N1 influenza A viruses (IAVs) containing hemagglutinin (HA) proteins with globular heads that differ substantially from seasonal strains results in a boost in broadly cross-reactive antibodies that bind to the HA stalk. Boosting these antibodies has become an attractive strategy for creating a universal IAV vaccine. Therefore, it was essential to determine whether vaccines containing H1N1 viruses whose head domains differ substantially compared to seasonal strains could also achieve this boost. METHODS: Prospective samples of subjects who had received the A/New Jersey/1976 (NJ/76) vaccine and healthy, age-matched controls were assessed for the presence of anti-HA stalk antibodies before and after receiving the A/California/04/2009 (Cal/09) vaccine between October 2009 and January 2010. RESULTS: Individuals who received either the NJ/76 vaccine or the Cal/09 vaccine experienced a robust boost in HA stalk-reactive, neutralizing antibodies similar to what has been observed in individuals infected with Cal/09. CONCLUSIONS: These results demonstrate that vaccines containing viruses whose HA head domains that differ substantially from seasonal strains are capable of boosting titers of HA stalk antibodies. Furthermore, anti-HA stalk antibodies elicited by vaccination appear to be long-lived and therefore could be targeted for the generation of a universal IAV vaccine.
BACKGROUND: Infection with pandemic H1N1 influenza A viruses (IAVs) containing hemagglutinin (HA) proteins with globular heads that differ substantially from seasonal strains results in a boost in broadly cross-reactive antibodies that bind to the HA stalk. Boosting these antibodies has become an attractive strategy for creating a universal IAV vaccine. Therefore, it was essential to determine whether vaccines containing H1N1 viruses whose head domains differ substantially compared to seasonal strains could also achieve this boost. METHODS: Prospective samples of subjects who had received the A/New Jersey/1976 (NJ/76) vaccine and healthy, age-matched controls were assessed for the presence of anti-HA stalk antibodies before and after receiving the A/California/04/2009 (Cal/09) vaccine between October 2009 and January 2010. RESULTS: Individuals who received either the NJ/76 vaccine or the Cal/09 vaccine experienced a robust boost in HA stalk-reactive, neutralizing antibodies similar to what has been observed in individuals infected with Cal/09. CONCLUSIONS: These results demonstrate that vaccines containing viruses whose HA head domains that differ substantially from seasonal strains are capable of boosting titers of HA stalk antibodies. Furthermore, anti-HA stalk antibodies elicited by vaccination appear to be long-lived and therefore could be targeted for the generation of a universal IAV vaccine.
Authors: Jonathan A McCullers; Lee-Ann Van De Velde; Kim J Allison; Kristen C Branum; Richard J Webby; Patricia M Flynn Journal: Clin Infect Dis Date: 2010-06-01 Impact factor: 9.079
Authors: Gui-Mei Li; Christopher Chiu; Jens Wrammert; Megan McCausland; Sarah F Andrews; Nai-Ying Zheng; Jane-Hwei Lee; Min Huang; Xinyan Qu; Srilatha Edupuganti; Mark Mulligan; Suman R Das; Jonathan W Yewdell; Aneesh K Mehta; Patrick C Wilson; Rafi Ahmed Journal: Proc Natl Acad Sci U S A Date: 2012-05-21 Impact factor: 11.205
Authors: G Neumann; T Watanabe; H Ito; S Watanabe; H Goto; P Gao; M Hughes; D R Perez; R Donis; E Hoffmann; G Hobom; Y Kawaoka Journal: Proc Natl Acad Sci U S A Date: 1999-08-03 Impact factor: 11.205
Authors: John C Kash; Li Qi; Vivien G Dugan; Brett W Jagger; Rachel J Hrabal; Matthew J Memoli; David M Morens; Jeffery K Taubenberger Journal: Influenza Other Respir Viruses Date: 2010-05-01 Impact factor: 4.380
Authors: C A Thomson; Y Wang; L M Jackson; M Olson; W Wang; A Liavonchanka; L Keleta; V Silva; S Diederich; R B Jones; J Gubbay; J Pasick; M Petric; François Jean; V G Allen; E G Brown; J M Rini; J W Schrader Journal: Front Immunol Date: 2012-05-08 Impact factor: 7.561
Authors: Florian Krammer; Rong Hai; Mark Yondola; Gene S Tan; Victor H Leyva-Grado; Alex B Ryder; Matthew S Miller; John K Rose; Peter Palese; Adolfo García-Sastre; Randy A Albrecht Journal: J Virol Date: 2014-01-08 Impact factor: 5.103
Authors: Wenqian He; Gene S Tan; Caitlin E Mullarkey; Amanda J Lee; Mannie Man Wai Lam; Florian Krammer; Carole Henry; Patrick C Wilson; Ali A Ashkar; Peter Palese; Matthew S Miller Journal: Proc Natl Acad Sci U S A Date: 2016-10-03 Impact factor: 11.205
Authors: James R R Whittle; Adam K Wheatley; Lan Wu; Daniel Lingwood; Masaru Kanekiyo; Steven S Ma; Sandeep R Narpala; Hadi M Yassine; Gregory M Frank; Jonathan W Yewdell; Julie E Ledgerwood; Chih-Jen Wei; Adrian B McDermott; Barney S Graham; Richard A Koup; Gary J Nabel Journal: J Virol Date: 2014-02-05 Impact factor: 5.103
Authors: Wenqian He; Caitlin E Mullarkey; J Andrew Duty; Thomas M Moran; Peter Palese; Matthew S Miller Journal: J Virol Date: 2015-01-14 Impact factor: 5.103
Authors: Wan Yang; Matthew J Cummings; Barnabas Bakamutumaho; John Kayiwa; Nicholas Owor; Barbara Namagambo; Timothy Byaruhanga; Julius J Lutwama; Max R O'Donnell; Jeffrey Shaman Journal: Epidemics Date: 2018-03-19 Impact factor: 4.396