title: Heterosubtypic immunity to H7N9 influenza virus in isogenic guinea pigs after infection with pandemic H1N1 virus.
abstract: Heterosubtypic immunity is defined as immune-mediated (partial) protection against an influenza virus induced by an influenza virus of another subtype to which the host has not previously been exposed. This cross-protective effect has not yet been demonstrated to the newly emerging avian influenza A viruses of the H7N9 subtype. Here, we assessed the induction of protective immunity to these viruses by infection with A(H1N1)pdm09 virus in a newly developed guinea pig model. To this end, ten female 12-16 week old strain 2 guinea pigs were inoculated intratracheally with either A(H1N1)pdm09 influenza virus or PBS (unprimed controls) followed 4 weeks later with an A/H7N9 influenza virus challenge. Nasal swabs were taken daily and animals from both groups were sacrificed on days 2 and 7 post inoculation (p.i.) with A/H7N9 virus and full necropsies were performed. Nasal virus excretion persisted until day 7 in unprimed control animals, whereas only two out of seven H1N1pdm09-primed animals excreted virus via the nose. Infectious virus was recovered from nasal turbinates, trachea and lung of all animals at day 2 p.i., but titers were lower for H1N1pdm09-primed animals, especially in the nasal turbinates. By day 7 p.i., relatively high virus titers were found in the nasal turbinates of all unprimed control animals but infectious virus was isolated from the nose of only one of four H1N1pdm09-primed animals. Animals of both groups developed inflammation of variable severity in the entire respiratory tract. Viral antigen positive cells were demonstrated in the nasal epithelium of both groups at day 2. The bronchi(oli) and alveoli of unprimed animals showed a moderate to strong positive signal at day 2, whereas H1N1pdm09-primed animals showed only minimal positivity. By day 7, only viral antigen positive cells were found after H7N9 virus infection in the nasal turbinates and the lungs of unprimed controls. Thus infection with H1N1pdm09 virus induced partially protective heterosubtypic immunity to H7N9 virus in (isogenic) guinea pigs that could not be attributed to cross-reactive virus neutralizing antibodies.
authors: Department of Viroscience, Erasmus Medical Centre, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.
authors: Lidewij C M
authors: LC
authors: Wiersma
authors: Department of Viroscience, Erasmus Medical Centre, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.
authors: Stella E
authors: SE
authors: Vogelzang-van Trierum
authors: Department of Viroscience, Erasmus Medical Centre, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.
authors: Joost H C M
authors: JH
authors: Kreijtz
authors: Department of Viroscience, Erasmus Medical Centre, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands; Viroclinics Biosciences B.V., Rotterdam Science Tower, Marconistraat 16, 3029 AK Rotterdam, The Netherlands.
authors: Geert
authors: G
authors: van Amerongen
authors: Department of Viroscience, Erasmus Medical Centre, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.
authors: Peter
authors: P
authors: van Run
authors: Department of Experimental Toxicology and Centre for Documentation and Evaluation of Alternatives to Animal Experiments, The Federal Institute for Risk Assessment, Diedersdorfer Weg 1, 12277 Berlin, Germany.
authors: Mechtild
authors: M
authors: Ladwig
authors: Department of Experimental Toxicology and Centre for Documentation and Evaluation of Alternatives to Animal Experiments, The Federal Institute for Risk Assessment, Diedersdorfer Weg 1, 12277 Berlin, Germany.
authors: Stefanie
authors: S
authors: Banneke
authors: Experimental Immunology, Robert Koch Institute, Nordufer 20, 13353 Berlin, Germany.
authors: Hubert
authors: H
authors: Schaefer
authors: Department of Viroscience, Erasmus Medical Centre, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.
authors: Ron A M
authors: RA
authors: Fouchier
authors: Department of Viroscience, Erasmus Medical Centre, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.
authors: Thijs
authors: T
authors: Kuiken
authors: Department of Viroscience, Erasmus Medical Centre, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands; Viroclinics Biosciences B.V., Rotterdam Science Tower, Marconistraat 16, 3029 AK Rotterdam, The Netherlands.
authors: Albert D M E
authors: AD
authors: Osterhaus
authors: Department of Viroscience, Erasmus Medical Centre, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands; Viroclinics Biosciences B.V., Rotterdam Science Tower, Marconistraat 16, 3029 AK Rotterdam, The Netherlands. Electronic address: g.rimmelzwaan@erasmusmc.nl.
authors: Guus F
authors: GF
authors: Rimmelzwaan
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000032:analysis; D056738:Cross Protection; D005260:Female; D006168:Guinea Pigs; D053118:Influenza A Virus, H1N1 Subtype; D064766:Influenza A Virus, H7N9 Subtype; D008168:Lung / Q000473:pathology / Q000821:virology; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D014132:Trachea / Q000473:pathology / Q000821:virology
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000956:Antigens, Viral
keywords: Heterosubtypic immunity; Influenza; Isogenic guinea pig