Development and pre-clinical evaluation of two LAIV strains against potentially pandemic H2N2 influenza virus.

H2N2 Influenza A caused the Asian flu pandemic in 1957, circulated for more than 10 years and disappeared from the human population after 1968. Given that people born after 1968 are naïve to H2N2, that the virus still circulates in wild birds and that this influenza subtype has a proven pandemic tra...

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Autores principales:	Irina Isakova-Sivak, Jørgen de Jonge, Tatiana Smolonogina, Andrey Rekstin, Geert van Amerongen, Harry van Dijken, Justin Mouthaan, Paul Roholl, Victoria Kuznetsova, Elena Doroshenko, Vadim Tsvetnitsky, Larisa Rudenko
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8bf254488d9e4ae3bd4006388b2ae3d6
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spelling	oai:doaj.org-article:8bf254488d9e4ae3bd4006388b2ae3d62021-11-25T06:07:17ZDevelopment and pre-clinical evaluation of two LAIV strains against potentially pandemic H2N2 influenza virus.1932-620310.1371/journal.pone.0102339https://doaj.org/article/8bf254488d9e4ae3bd4006388b2ae3d62014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25058039/?tool=EBIhttps://doaj.org/toc/1932-6203H2N2 Influenza A caused the Asian flu pandemic in 1957, circulated for more than 10 years and disappeared from the human population after 1968. Given that people born after 1968 are naïve to H2N2, that the virus still circulates in wild birds and that this influenza subtype has a proven pandemic track record, H2N2 is regarded as a potential pandemic threat. To prepare for an H2N2 pandemic, here we developed and tested in mice and ferrets two live attenuated influenza vaccines based on the haemagglutinins of the two different H2N2 lineages that circulated at the end of the cycle, using the well characterized A/Leningrad/134/17/57 (H2N2) master donor virus as the backbone. The vaccine strains containing the HA and NA of A/California/1/66 (clade 1) or A/Tokyo/3/67 (clade 2) showed a temperature sensitive and cold adapted phenotype and a reduced reproduction that was limited to the respiratory tract of mice, suggesting that the vaccines may be safe for use in humans. Both vaccine strains induced haemagglutination inhibition titers in mice. Vaccination abolished virus replication in the nose and lung and protected mice from weight loss after homologous and heterologous challenge with the respective donor wild type strains. In ferrets, the live attenuated vaccines induced high virus neutralizing, haemagglutination and neuraminidase inhibition titers, however; the vaccine based on the A/California/1/66 wt virus induced higher homologous and better cross-reactive antibody responses than the A/Tokyo/3/67 based vaccine. In line with this observation, was the higher virus reduction observed in the throat and nose of ferrets vaccinated with this vaccine after challenge with either of the wild type donor viruses. Moreover, both vaccines clearly reduced the infection-induced rhinitis observed in placebo-vaccinated ferrets. The results favor the vaccine based on the A/California/1/66 isolate, which will be evaluated in a clinical study.Irina Isakova-SivakJørgen de JongeTatiana SmolonoginaAndrey RekstinGeert van AmerongenHarry van DijkenJustin MouthaanPaul RohollVictoria KuznetsovaElena DoroshenkoVadim TsvetnitskyLarisa RudenkoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 7, p e102339 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Irina Isakova-Sivak Jørgen de Jonge Tatiana Smolonogina Andrey Rekstin Geert van Amerongen Harry van Dijken Justin Mouthaan Paul Roholl Victoria Kuznetsova Elena Doroshenko Vadim Tsvetnitsky Larisa Rudenko Development and pre-clinical evaluation of two LAIV strains against potentially pandemic H2N2 influenza virus.
description	H2N2 Influenza A caused the Asian flu pandemic in 1957, circulated for more than 10 years and disappeared from the human population after 1968. Given that people born after 1968 are naïve to H2N2, that the virus still circulates in wild birds and that this influenza subtype has a proven pandemic track record, H2N2 is regarded as a potential pandemic threat. To prepare for an H2N2 pandemic, here we developed and tested in mice and ferrets two live attenuated influenza vaccines based on the haemagglutinins of the two different H2N2 lineages that circulated at the end of the cycle, using the well characterized A/Leningrad/134/17/57 (H2N2) master donor virus as the backbone. The vaccine strains containing the HA and NA of A/California/1/66 (clade 1) or A/Tokyo/3/67 (clade 2) showed a temperature sensitive and cold adapted phenotype and a reduced reproduction that was limited to the respiratory tract of mice, suggesting that the vaccines may be safe for use in humans. Both vaccine strains induced haemagglutination inhibition titers in mice. Vaccination abolished virus replication in the nose and lung and protected mice from weight loss after homologous and heterologous challenge with the respective donor wild type strains. In ferrets, the live attenuated vaccines induced high virus neutralizing, haemagglutination and neuraminidase inhibition titers, however; the vaccine based on the A/California/1/66 wt virus induced higher homologous and better cross-reactive antibody responses than the A/Tokyo/3/67 based vaccine. In line with this observation, was the higher virus reduction observed in the throat and nose of ferrets vaccinated with this vaccine after challenge with either of the wild type donor viruses. Moreover, both vaccines clearly reduced the infection-induced rhinitis observed in placebo-vaccinated ferrets. The results favor the vaccine based on the A/California/1/66 isolate, which will be evaluated in a clinical study.
format	article
author	Irina Isakova-Sivak Jørgen de Jonge Tatiana Smolonogina Andrey Rekstin Geert van Amerongen Harry van Dijken Justin Mouthaan Paul Roholl Victoria Kuznetsova Elena Doroshenko Vadim Tsvetnitsky Larisa Rudenko
author_facet	Irina Isakova-Sivak Jørgen de Jonge Tatiana Smolonogina Andrey Rekstin Geert van Amerongen Harry van Dijken Justin Mouthaan Paul Roholl Victoria Kuznetsova Elena Doroshenko Vadim Tsvetnitsky Larisa Rudenko
author_sort	Irina Isakova-Sivak
title	Development and pre-clinical evaluation of two LAIV strains against potentially pandemic H2N2 influenza virus.
title_short	Development and pre-clinical evaluation of two LAIV strains against potentially pandemic H2N2 influenza virus.
title_full	Development and pre-clinical evaluation of two LAIV strains against potentially pandemic H2N2 influenza virus.
title_fullStr	Development and pre-clinical evaluation of two LAIV strains against potentially pandemic H2N2 influenza virus.
title_full_unstemmed	Development and pre-clinical evaluation of two LAIV strains against potentially pandemic H2N2 influenza virus.
title_sort	development and pre-clinical evaluation of two laiv strains against potentially pandemic h2n2 influenza virus.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/8bf254488d9e4ae3bd4006388b2ae3d6
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Development and pre-clinical evaluation of two LAIV strains against potentially pandemic H2N2 influenza virus.

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