Intranasal Administration of Cold-Adapted Live-Attenuated Eurasian Avian-like H1N1 Vaccine Candidate Confers Protection Against Different-Lineage H1N1 Viruses in Mice
Background/Objectives: Eurasian avian-like (EA) H1N1 swine influenza viruses, with their persistent evolution and zoonotic potential, seriously threaten both swine and human health. The objective was to develop an effective vaccine against these viruses. Methods: A cold-adapted, temperature-sensitiv...
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2025-05-01
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| author | Qiu Zhong Zuchen Song Fei Meng Yanwen Wang Yijie Zhang Zijian Feng Yali Zhang Yujia Zhai Yan Chen Chuanling Qiao Hualan Chen Huanliang Yang |
| author_facet | Qiu Zhong Zuchen Song Fei Meng Yanwen Wang Yijie Zhang Zijian Feng Yali Zhang Yujia Zhai Yan Chen Chuanling Qiao Hualan Chen Huanliang Yang |
| author_sort | Qiu Zhong |
| collection | DOAJ |
| description | Background/Objectives: Eurasian avian-like (EA) H1N1 swine influenza viruses, with their persistent evolution and zoonotic potential, seriously threaten both swine and human health. The objective was to develop an effective vaccine against these viruses. Methods: A cold-adapted, temperature-sensitive live-attenuated influenza vaccine (LAIV) candidate, GX18<i>ca</i>, was developed. It was derived from the wild-type EA H1N1 strain A/swine/Guangxi/18/2011 (GX18) through serial passaging in embryonated eggs at temperatures decreasing from 33 °C to 25 °C. Its characteristics were studied in mice, including attenuation, immune responses (mucosal IgA, serum IgG, IFN-γ+ CD4<sup>+</sup>/CD8<sup>+</sup> T-cell responses), and protective efficacy against homologous (GX18), heterologous EA H1N1 (LN972), and human 2009/H1N1 (SC1) viruses. Results: GX18<i>ca</i> showed cold-adapted and temperature-sensitive phenotypes. In mice, it was attenuated, with viral titers in the nasal turbinates and lungs reduced 1000–10,000-fold compared to the wild-type strain, and it cleared by day 5 post infection. Intranasal immunization elicited strong cross-reactive immune responses. Mucosal IgA had broad reactivity, and serum IgG titers reached high levels. IFN-γ+ CD4<sup>+/</sup>CD8<sup>+</sup> T-cell responses were detected against all the tested viruses. A single dose of GX18<i>ca</i> fully protected against GX18 and LN972 challenges, and two doses significantly reduced SC1 lung viral loads, preventing mortality and weight loss. Conclusions: GX18<i>ca</i> is a promising LAIV candidate. It can induce broad immunity, addressing the cross-protection gaps against evolving EA H1N1 SIVs and zoonotic H1N1 variants, which is crucial for swine influenza control and pandemic preparedness. |
| format | Article |
| id | doaj-art-0aa70244a88a4a9ca13f0fb4ed9cd25d |
| institution | Matheson Library |
| issn | 2076-393X |
| language | English |
| publishDate | 2025-05-01 |
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| series | Vaccines |
| spelling | doaj-art-0aa70244a88a4a9ca13f0fb4ed9cd25d2025-06-25T14:30:01ZengMDPI AGVaccines2076-393X2025-05-0113659610.3390/vaccines13060596Intranasal Administration of Cold-Adapted Live-Attenuated Eurasian Avian-like H1N1 Vaccine Candidate Confers Protection Against Different-Lineage H1N1 Viruses in MiceQiu Zhong0Zuchen Song1Fei Meng2Yanwen Wang3Yijie Zhang4Zijian Feng5Yali Zhang6Yujia Zhai7Yan Chen8Chuanling Qiao9Hualan Chen10Huanliang Yang11State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, ChinaState Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, ChinaState Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, ChinaState Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, ChinaState Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, ChinaState Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, ChinaState Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, ChinaState Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, ChinaState Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, ChinaState Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, ChinaState Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, ChinaState Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, ChinaBackground/Objectives: Eurasian avian-like (EA) H1N1 swine influenza viruses, with their persistent evolution and zoonotic potential, seriously threaten both swine and human health. The objective was to develop an effective vaccine against these viruses. Methods: A cold-adapted, temperature-sensitive live-attenuated influenza vaccine (LAIV) candidate, GX18<i>ca</i>, was developed. It was derived from the wild-type EA H1N1 strain A/swine/Guangxi/18/2011 (GX18) through serial passaging in embryonated eggs at temperatures decreasing from 33 °C to 25 °C. Its characteristics were studied in mice, including attenuation, immune responses (mucosal IgA, serum IgG, IFN-γ+ CD4<sup>+</sup>/CD8<sup>+</sup> T-cell responses), and protective efficacy against homologous (GX18), heterologous EA H1N1 (LN972), and human 2009/H1N1 (SC1) viruses. Results: GX18<i>ca</i> showed cold-adapted and temperature-sensitive phenotypes. In mice, it was attenuated, with viral titers in the nasal turbinates and lungs reduced 1000–10,000-fold compared to the wild-type strain, and it cleared by day 5 post infection. Intranasal immunization elicited strong cross-reactive immune responses. Mucosal IgA had broad reactivity, and serum IgG titers reached high levels. IFN-γ+ CD4<sup>+/</sup>CD8<sup>+</sup> T-cell responses were detected against all the tested viruses. A single dose of GX18<i>ca</i> fully protected against GX18 and LN972 challenges, and two doses significantly reduced SC1 lung viral loads, preventing mortality and weight loss. Conclusions: GX18<i>ca</i> is a promising LAIV candidate. It can induce broad immunity, addressing the cross-protection gaps against evolving EA H1N1 SIVs and zoonotic H1N1 variants, which is crucial for swine influenza control and pandemic preparedness.https://www.mdpi.com/2076-393X/13/6/596Eurasian avian-like H1N1 swine influenza viruscold-adapted vaccineintranasal administrationprotective efficacy |
| spellingShingle | Qiu Zhong Zuchen Song Fei Meng Yanwen Wang Yijie Zhang Zijian Feng Yali Zhang Yujia Zhai Yan Chen Chuanling Qiao Hualan Chen Huanliang Yang Intranasal Administration of Cold-Adapted Live-Attenuated Eurasian Avian-like H1N1 Vaccine Candidate Confers Protection Against Different-Lineage H1N1 Viruses in Mice Vaccines Eurasian avian-like H1N1 swine influenza virus cold-adapted vaccine intranasal administration protective efficacy |
| title | Intranasal Administration of Cold-Adapted Live-Attenuated Eurasian Avian-like H1N1 Vaccine Candidate Confers Protection Against Different-Lineage H1N1 Viruses in Mice |
| title_full | Intranasal Administration of Cold-Adapted Live-Attenuated Eurasian Avian-like H1N1 Vaccine Candidate Confers Protection Against Different-Lineage H1N1 Viruses in Mice |
| title_fullStr | Intranasal Administration of Cold-Adapted Live-Attenuated Eurasian Avian-like H1N1 Vaccine Candidate Confers Protection Against Different-Lineage H1N1 Viruses in Mice |
| title_full_unstemmed | Intranasal Administration of Cold-Adapted Live-Attenuated Eurasian Avian-like H1N1 Vaccine Candidate Confers Protection Against Different-Lineage H1N1 Viruses in Mice |
| title_short | Intranasal Administration of Cold-Adapted Live-Attenuated Eurasian Avian-like H1N1 Vaccine Candidate Confers Protection Against Different-Lineage H1N1 Viruses in Mice |
| title_sort | intranasal administration of cold adapted live attenuated eurasian avian like h1n1 vaccine candidate confers protection against different lineage h1n1 viruses in mice |
| topic | Eurasian avian-like H1N1 swine influenza virus cold-adapted vaccine intranasal administration protective efficacy |
| url | https://www.mdpi.com/2076-393X/13/6/596 |
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