Radvak Peter, Kosikova Martina, Kuo Yuan-Chia, Li Xing, Garner Richard, Schmeisser Falko, Kosik Ivan, Ye Zhiping, Weir Jerry P, Yewdell Jonathan W, Xie Hang
Laboratory of Pediatric and Respiratory Viral Diseases, Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD, USA.
Laboratory of DNA Viruses, Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD, USA.
NPJ Vaccines. 2021 Feb 26;6(1):30. doi: 10.1038/s41541-021-00295-7.
Avian influenza A(H7N9) epidemics have a fatality rate of approximately 40%. Previous studies reported that low pathogenic avian influenza (LPAI)-derived candidate vaccine viruses (CVVs) are poorly immunogenic. Here, we assess the immunogenicity and efficacy of a highly pathogenic avian influenza (HPAI) A/Guangdong/17SF003/2016 (GD/16)-extracted hemagglutinin (eHA) vaccine. GD/16 eHA induces robust H7-specific antibody responses in mice with a marked adjuvant antigen-sparing effect. Mice immunized with adjuvanted GD/16 eHA are protected from the lethal LPAI and HPAI H7N9 challenges, in stark contrast to low antibody titers and high mortality in mice receiving adjuvanted LPAI H7 eHAs. The protection correlates well with the magnitude of the H7-specific antibody response (IgG and microneutralization) or HA group 2 stem-specific IgG. Inclusion of adjuvanted GD/16 eHA in heterologous prime-boost improves the immunogenicity and protection of LPAI H7 HAs in mice. Our findings support the inclusion of GD/16-derived CVV in the pandemic preparedness vaccine stockpile.
甲型H7N9禽流感疫情的病死率约为40%。此前的研究报告称,低致病性禽流感(LPAI)衍生的候选疫苗病毒(CVV)免疫原性较差。在此,我们评估了一种高致病性禽流感(HPAI)A/广东/17SF003/2016(GD/16)提取的血凝素(eHA)疫苗的免疫原性和效力。GD/16 eHA在小鼠中诱导出强烈的H7特异性抗体反应,并具有显著的佐剂抗原节省效应。用佐剂GD/16 eHA免疫的小鼠可免受致死性LPAI和HPAI H7N9攻击,这与接受佐剂LPAI H7 eHA的小鼠抗体滴度低和死亡率高形成鲜明对比。这种保护与H7特异性抗体反应(IgG和微量中和)或HA第2组茎特异性IgG的强度密切相关。在异源初免-加强免疫中加入佐剂GD/16 eHA可提高小鼠中LPAI H7 HA的免疫原性和保护作用。我们的研究结果支持将GD/16衍生的CVV纳入大流行防范疫苗储备。