Preclinical evaluation of the safety and pathogenicity of a live attenuated recombinant influenza A/H7N9 seed strain and corresponding MF59-adjuvanted split vaccine

Ou, Huilin; Yao, Wei; Wu, Nanping; Wang, Frederick X.C.; Weng, Tian-Hao; Han, Chengcong; Lu, Xiangyun; Yu, Dongshan; Wu, Haibo; Cheng, Linfang; Chen, Honglin; Yao, Hang‐Ping; Li, Lanjuan

doi:10.18632/oncotarget.12746

Cited by 10 publications

(7 citation statements)

References 27 publications

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“…Moreover, we performed acute toxicity, repeated dose toxicity, and active systemic anaphylaxis tests to evaluate the safety of our H7N9 vaccine in mice. This vaccine completed the immunogenicity and safety testing [9]. …”

Section: Introductionmentioning

confidence: 99%

The Protective Effects of the A/ZJU01/ PR8/2013 Split H7N9 Avian Influenza Vaccine Against Highly Pathogenic H7N9 in BALB/c Mice

Deng

et al. 2018

Cell Physiol Biochem

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Background/Aims: Since the first case of novel H7N9 infection was reported, China has experienced five epidemics of H7N9. During the fifth wave, a highly pathogenic H7N9 strain emerged. In order to assess whether the H7N9 vaccine based on A/Zhejiang/DTID-ZJU01/2013(H7N9) was effective in protecting against highly pathogenic H7N9, we conducted this study. Methods: Groups of mice were immunized twice by intraperitoneal injection with 500 µl of either split vaccine alone or MF59-adjuvanted vaccine. Serum was collected 2 weeks after the second vaccine booster. The hemagglutinin inhibition test was conducted on vaccine seed and highly pathogenic H7N9 to evaluate the neutralization of highly pathogenic H7N9. We also immunized mice and challenged them with highly pathogenic H7N9. Mice were observed for illness, weight loss, and death at 1 week and 2 weeks post-infection. Then, the mice were sacrificed and lungs were removed. Antibody responses were assessed and pathological changes in the lung tissue were evaluated. Results: The ability of serum to neutralize highly pathogenic H7N9 was reduced. In mice, highly pathogenic H7N9 was more virulent than A/Zhejiang/DTID-ZJU01/2013(H7N9). After challenge with highly pathogenic H7N9, all mice died while mice challenged with A/Zhejiang/DTID-ZJU01/2013(H7N9) all recovered. The A/ZJU01/PR8/2013 split H7N9 avian influenza vaccine was able to protect against infection with highly pathogenic H7N9 in mice, with or without MF59. Moreover, H7N9 vaccine adjuvanted with MF59 produced high antibody levels, which lead to better protection. Conclusions: The A/ZJU01/PR8/2013 split H7N9 avian influenza vaccine based on A/Zhejiang/DTID-ZJU01/2013(H7N9) is effective in protecting against highly pathogenic H7N9. H7N9 vaccine adjuvanted with MF59 offers better protection against infection with highly pathogenic H7N9. In order to make the H7N9 vaccine applicable to humans, further clinical trials are required to evaluate MF59 adjuvanted vaccine. Meanwhile, the vaccine strain should be updated based on the highly pathogenic H7N9 gene sequence.

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Section: Introductionmentioning

confidence: 99%

The Protective Effects of the A/ZJU01/ PR8/2013 Split H7N9 Avian Influenza Vaccine Against Highly Pathogenic H7N9 in BALB/c Mice

Deng

et al. 2018

Cell Physiol Biochem

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“…Other H7N9 vaccine candidates have been tested in preclinical studies and have shown to be immunogenic and protective in animal models. These vaccines include H7N9 split vaccines using different adjuvants like SWE (an oil-in-water adjuvant) 26 and MF59 27 , 28 or non-adjuvanted split vaccines 29 . Other approaches are based on live attenuated virus vaccines 30 , 31 , recombinant H7 HA formulations 32 , or mRNA 33 , 34 .…”

Section: Discussionmentioning

confidence: 99%

AS03-adjuvanted H7N9 inactivated split virion vaccines induce cross-reactive and protective responses in ferrets

et al. 2021

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Human infections with avian H7N9 subtype influenza viruses are a major public health concern and vaccines against H7N9 are urgently needed for pandemic preparedness. In early 2013, novel H7N9 influenza viruses emerged in China that caused about 1600 human cases of infection with a high associated case fatality rate. In this study, two H7N9 split virion vaccines with or without AS03 adjuvant were tested in the naive ferret model. Serological analyses demonstrated that homologous hemagglutination inhibition and microneutralization antibody titers were detectable in the ferrets after the first immunization with the AS03-adjuvanted vaccines that were further boosted by the second immunization. In addition, heterologous antibody titers against older H7 subtype viruses of the North American lineage (H7N7, H7N3) and newer H7 subtype viruses of the Eurasian lineage (H7N9) were detected in the animals receiving the AS03-adjuvanted vaccines. Animals receiving two immunizations of the AS03-adjuvanted vaccines were protected from weight loss and fever in the homologous challenge study and had no detectable virus in throat or lung samples. In addition, microscopic examination post-challenge showed animals immunized with the AS03-adjuvanted vaccines had the least signs of lung injury and inflammation, consistent with the greater relative efficacy of the adjuvanted vaccines. In conclusion, this study demonstrated that the AS03-adjuvanted H7N9 vaccines elicited high levels of homologous and heterologous antibodies and protected against H7N9 virus damage post-challenge.

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“…All serum samples were treated with receptor destroying enzyme [ 9 ]. Prior to HI testing, a two-fold serial dilution series of serum was mixed 1:1 with four hemagglutinating units of virus (wild type H7N9 virus A/Zhejiang/DTID-ZJU01/2013 (H7N9)) and incubated at 37°C for 1 h. Subsequently, 50 μL 1% chicken erythrocytes were added, mixed, and incubated for 1 h at 4°C; all agglutination patterns were read within 10 min.…”

Section: Methodsmentioning

confidence: 99%

“…It has the advantage of rapid preparation and rapid amplification. Accordingly, we verified that the recombinant clones harbor the desirable characteristics, including lower virulence and transmissibility, as a vaccine strain [ 9 ]. Additionally, the oil-in-water adjuvant MF59, which we have paired with our split virus vaccine, has been reported to be safe, well-tolerated, and able to improve the antibody response, permit dose sparing, and lower the antigen dose required to induce protection [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Longevity of protective immune responses induced by a split influenza A (H7N9) vaccine mixed with MF59 adjuvant in BALB/c mice

Yao²,

et al. 2017

Oncotarget

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The influenza virus is a serious threat to public health worldwide. A novel avian influenza A (H7N9) virus with a mortality rate of approximately 30% has been identified as an unusually dangerous virus for humans by the World Health Organization. Pathogenic H7N9 continue to represent a public health concern, and several candidate vaccines are currently in development. We generated candidate H7N9 vaccine strains using reverse genetics, consisting of hemagglutinin and neuraminidase genes derived from a human H7N9 virus and the remaining genes from the PR8 (A/PuertoRico/8/34 (H1N1)) virus. This H7N9 vaccine exhibited superior efficacy when combined with MF59 compared to other adjuvants. Immunized BALB/c mice were followed to determine the duration of the protective immune response. Antibody levels decreased to between one-half and one-eighth of the peak values four months after the final dose of the vaccine. Previously vaccinated mice received an A/Zhejiang/DTID-ZJU01/2013 H7N9 challenge six months post-vaccination, and all remained protected. We also verified that MF59 enhanced the HI, MN, and IgG antibody titers to influenza antigens. The humoral immune response and Th2 cytokine production following influenza challenge was potently induced in the animals that received the split vaccine. Therefore, the split H7N9 influenza vaccine with the MF59 adjuvant could effectively induce antibody production and protect mice from H7N9 virus challenge even after six months.

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Preclinical evaluation of the safety and pathogenicity of a live attenuated recombinant influenza A/H7N9 seed strain and corresponding MF59-adjuvanted split vaccine

Cited by 10 publications

References 27 publications

The Protective Effects of the A/ZJU01/ PR8/2013 Split H7N9 Avian Influenza Vaccine Against Highly Pathogenic H7N9 in BALB/c Mice

The Protective Effects of the A/ZJU01/ PR8/2013 Split H7N9 Avian Influenza Vaccine Against Highly Pathogenic H7N9 in BALB/c Mice

AS03-adjuvanted H7N9 inactivated split virion vaccines induce cross-reactive and protective responses in ferrets

Longevity of protective immune responses induced by a split influenza A (H7N9) vaccine mixed with MF59 adjuvant in BALB/c mice

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