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Mini-hemagglutinin vaccination induces cross-reactive antibodies in pre-exposed NHP that protect mice against lethal influenza challenge. 2018
Joan E M van der Lubbe, and
Jeroen Huizingh, and
Johan W A Verspuij, and
Lisanne Tettero, and
Sonja P R Schmit-Tillemans, and
Petra Mooij, and
Daniella Mortier, and
Gerrit Koopman, and
Willy M J M Bogers, and
Liesbeth Dekking, and
Wim Meijberg, and
Ted Kwaks, and
Boerries Brandenburg, and
Jeroen T B M Tolboom, and
Hanneke Schuitemaker, and
Ramon Roozendaal, and
Harmjan Kuipers, and
Roland C Zahn
Janssen Vaccines and Prevention, Pharmaceutical Companies of Johnson and Johnson, Archimedesweg 4-6, 2333 CN Leiden, The Netherlands.
Seasonal vaccines are currently the most effective countermeasure against influenza. However, seasonal vaccines are only effective against strains closely related to the influenza strains contained in the vaccine. Recently a new hemagglutinin (HA) stem-based antigen, the so-called "mini-HA", has been shown to induce a cross-protective immune response in influenza-naive mice and non-human primates (NHP). However, prior exposure to influenza can have a profound effect on the immune response to subsequent influenza infection and the protective efficacy of vaccination. Here we show that mini-HA, compared to a trivalent influenza vaccine (TIV), elicits a broadened influenza-specific humoral immune response in NHP previously exposed to influenza. Serum transfer experiments showed that antibodies induced by both mini-HA and seasonal vaccine protected mice against lethal challenge with a H1N1 influenza strain heterologous to the H1 HA included in the TIV. However, antibodies elicited by mini-HA showed an additional benefit of protecting mice against lethal heterosubtypic H5N1 influenza challenge, associated with H5 HA-specific functional antibodies.
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