The use of human monoclonal antibodies to inform and enhance influenza vaccine virus selection.

使用人单克隆抗体来告知和增强流感疫苗病毒的选择。

• 批准号: MR/P021336/1
• 负责人: John McCauley
• 金额: $ 127.81万
• 依托单位: The Francis Crick Institute
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FP021336%2F1
• 关键词: use; human; monoclonal; antibodies; inform

Influenza infections each year cause a major burden of sickness and death (greater than 250,000 deaths each year world wide). The most effective means of reducing illness caused by influenza is by vaccination. The influenza virus evolves by changing its surface proteins each year in response to selective pressure from the human antibody response. The World Health Organisation coordinates a massive effort to monitor the evolution of influenza around the world to try and identify the viruses that are most likely to cause infections in the coming years, and select the best candidates for manufacture into a vaccine. The methods used to do this are both new, by sequencing virus genes to monitor genetic changes, and old, by testing the antibodies that ferrets make to candidate vaccine viruses for cross-reactivity with circulating strains. Ferret antibodies are traditionally used because these animals are susceptible to influenza infections in a way similar to humans. Overall the effectiveness (reduction in risk of becoming ill with influenza) of the vaccines selected by these methods is quite poor at ~54%, so there is room for improvement. Recent technical developments have provided a new method to analyse the evolution of influenza that uses human monoclonal antibodies. It is these human antibodies that are thought to be driving the evolution of influenza in nature. We have shown that human antibodies isolated from vaccinated or infected individuals can detect changes in the virus that the ferret antibodies miss. In addition the changes that human antibodies detect frequently correlate with the changes that are appearing in the influenza viruses currently circulating in the human population. We propose to develop panels of human monoclonal antibodies that can help predict the future evolution of the virus, which will be distributed to the WHO Collaborating Centres around the world, for comparison to the standard ferret antibodies to see if this new technology can improve vaccine selection.

流感感染每年造成重大疾病和死亡负担（全世界每年死亡人数超过25万人）。减少流感引起的疾病的最有效方法是接种疫苗。流感病毒每年通过改变其表面蛋白来进化，以应对人类抗体反应的选择性压力。世界卫生组织协调了一项大规模的工作，以监测全球流感的演变，试图确定未来几年最有可能引起感染的病毒，并选择最佳候选病毒生产疫苗。用于此目的的方法既有新方法（通过对病毒基因进行测序来监测遗传变化），也有老方法（通过测试雪貂对候选疫苗病毒产生的抗体，以确定其与流行毒株的交叉反应性）。传统上使用雪貂抗体是因为这些动物对流感感染的易感性与人类相似。总的来说，通过这些方法选择的疫苗的有效性（降低患流感的风险）相当差，约为54%，因此还有改进的余地。最近的技术发展提供了一种利用人单克隆抗体分析流感演变的新方法。正是这些人类抗体被认为推动了流感在自然界的进化。我们已经证明，从接种疫苗或受感染的个体中分离出的人抗体可以检测出雪貂抗体没有检测到的病毒变化。此外，人抗体检测到的变化经常与目前在人群中传播的流感病毒中出现的变化相关。我们建议开发可帮助预测病毒未来演变的人类单克隆抗体组，这些抗体将分发给世界各地的世卫组织合作中心，以便与标准雪貂抗体进行比较，以了解这项新技术是否可以改进疫苗选择。

项目成果

Breadth and function of antibody response to acute SARS-CoV-2 infection in humans.

• DOI: 10.1371/journal.ppat.1009352
• 发表时间: 2021-03
• 期刊: PLoS pathogens
• 影响因子: 6.7
• 作者: Huang KA;Tan TK;Chen TH;Huang CG;Harvey R;Hussain S;Chen CP;Harding A;Gilbert-Jaramillo J;Liu X;Knight M;Schimanski L;Shih SR;Lin YC;Cheng CY;Cheng SH;Huang YC;Lin TY;Jan JT;Ma C;James W;Daniels RS;McCauley JW;Rijal P;Townsend AR
• 通讯作者: Townsend AR

Protective porcine influenza virus-specific monoclonal antibodies recognize similar haemagglutinin epitopes as humans.

• DOI: 10.1371/journal.ppat.1009330
• 发表时间: 2021-03
• 期刊: PLoS pathogens
• 影响因子: 6.7
• 作者: Holzer B;Rijal P;McNee A;Paudyal B;Martini V;Clark B;Manjegowda T;Salguero FJ;Bessell E;Schwartz JC;Moffat K;Pedrera M;Graham SP;Noble A;Bonnet-Di Placido M;La Ragione RM;Mwangi W;Beverley P;McCauley JW;Daniels RS;Hammond JA;Townsend AR;Tchilian E
• 通讯作者: Tchilian E

Simultaneous Aerosol and Intramuscular Immunization with Influenza Vaccine Induces Powerful Protective Local T Cell and Systemic Antibody Immune Responses in Pigs.

• DOI: 10.4049/jimmunol.2001086
• 发表时间: 2021-02-01
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Martini V;Paudyal B;Chrun T;McNee A;Edmans M;Atangana Maze E;Clark B;Nunez A;Dolton G;Sewell A;Beverley P;MacLoughlin R;Townsend A;Tchilian E
• 通讯作者: Tchilian E

Broadly inhibiting anti-neuraminidase monoclonal antibodies induced by trivalent influenza vaccine and H7N9 infection in humans

广泛抑制三价流感疫苗和人 H7N9 感染诱导的抗神经氨酸酶单克隆抗体

• DOI: 10.1101/682450
• 发表时间: 2019
• 作者: Rijal P

A COVID-19 vaccine candidate using SpyCatcher multimerization of the SARS-CoV-2 spike protein receptor-binding domain induces potent neutralising antibody responses.

• DOI: 10.1038/s41467-020-20654-7
• 发表时间: 2021-01-22
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Tan TK;Rijal P;Rahikainen R;Keeble AH;Schimanski L;Hussain S;Harvey R;Hayes JWP;Edwards JC;McLean RK;Martini V;Pedrera M;Thakur N;Conceicao C;Dietrich I;Shelton H;Ludi A;Wilsden G;Browning C;Zagrajek AK;Bialy D;Bhat S;Stevenson-Leggett P;Hollinghurst P;Tully M;Moffat K;Chiu C;Waters R;Gray A;Azhar M;Mioulet V;Newman J;Asfor AS;Burman A;Crossley S;Hammond JA;Tchilian E;Charleston B;Bailey D;Tuthill TJ;Graham SP;Duyvesteyn HME;Malinauskas T;Huo J;Tree JA;Buttigieg KR;Owens RJ;Carroll MW;Daniels RS;McCauley JW;Stuart DI;Huang KA;Howarth M;Townsend AR
• 通讯作者: Townsend AR