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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25058039/?tool=EBI |
| _version_ | 1819319342196588544 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-24T11:02:09Z |
| format | Article |
| id | doaj.art-8bf254488d9e4ae3bd4006388b2ae3d6 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-24T11:02:09Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-8bf254488d9e4ae3bd4006388b2ae3d62022-12-21T16:58:41ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0197e10233910.1371/journal.pone.0102339Development and pre-clinical evaluation of two LAIV strains against potentially pandemic H2N2 influenza virus.Irina Isakova-SivakJørgen de JongeTatiana SmolonoginaAndrey RekstinGeert van AmerongenHarry van DijkenJustin MouthaanPaul RohollVictoria KuznetsovaElena DoroshenkoVadim TsvetnitskyLarisa RudenkoH2N2 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.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25058039/?tool=EBI |
| spellingShingle | 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. PLoS ONE |
| title | 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_short | 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 |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25058039/?tool=EBI |
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