Immunity to respiratory tract pathogens-version 1
Research type
Research Study
Full title
Investigation of immune responses to respiratory tract pathogens and vaccines in adeno-tonsillar cells from humans
IRAS ID
158180
Contact name
Qibo Zhang
Contact email
Duration of Study in the UK
3 years, 11 months, 30 days
Research summary
Research Summary
Diseases caused by micro-organisms which infect the upper respiratory tract result in the deaths of millions of people worldwide each year. Respiratory pathogens, such as streptococcus pneumoniae, staphylococcus aureus, influenza virus and respiratory syncytial virus (RSV) cause significant morbidity and mortality in the form of respiratory failure or sepsis. The search for effective new vaccines against these pathogens or to improve upon existing ones is a priority.
Most of the respiratory tract pathogens initially infect human nasopharynx, therefore intranasal vaccination (such as the newly introduced influenza nasal vaccine in UK) is a promising preventative strategy against respiratory infection and invasive disease. It is generally thought that if a vaccine can induce an immune response at the site of initial infection, it will provide better protection. An additional benefit is that a nasally delivered vaccine may be more acceptable than a vaccine requiring an injection.
Human adenoids and tonsils are located at the entry sites of the respiratory pathogens described above. They are important immune organs against these bacteria and viruses. Using immune cells from these tissues, we can study how these immune tissues work to fight against infection, therefore to inform us design more effective vaccines, such as intranasal vaccines, against respiratory infections. Based on our recent studies, we have established a very useful cell culture system using the adenotonsillar cells to study the immune responses to respiratory pathogens and vaccine antigens. This culture system has the advantages of mimicking human in vivo immune responses and being more relevant than animal models.
In this project, we will study the immune responses in adenotonsillar cells to these pathogens and a number of novel candidate vaccines against the pathogens (eg.pneumococcus, staphylococcus, influenza and RSV viruses), so to inform the development of more effective vaccines in humans against these serious respiratory tract infections.Summary of Results
We have studied immune responses to several key human respiratory tract pathogens and novel vaccines using adeno-tonsillar cells from children (n=90) and adults (n=50). The pathogens and related vaccines include influenza and RSV viruses, pneumococcus and staphylococcus. The results have been published in a number of international journal papers as attached below. The data obtained from these studies provide important information on human mucosal immunity in the upper airway to these key pathogens and antigens to inform new vaccination strategies against the infections.
Published papers from the study:
1 Sharwani K, Sharma R, Krishnan M, Temperton NA, McNamara PS, Cunliffe NA, Turtle L, Zhang Q. Detection of serum cross-reactive antibodies and memory response to SARS-CoV-2 in pre-pandemic and post-COVID-19 convalescent samples. J Infect Dis 2021. Doi: 10.1093/infdis/jiab333.2 Xu R, Shears RK, Sharma R, Krishna M, Webb C, Ali R, Wei X, Kadioglu A, Zhang Q. IL-35 is critical in suppressing superantigenic Staphylococcus aureus-driven inflammatory Th17 responses in human nasopharynx-associated lymphoid tissue. Mucosal Immunology Jan 2020. doi:10.1038/s41385-019-0246-1.
3 Saengchoowong S, Khongnomnan K, Poomipak W, Praianantathavorn K, Poovorawan Y, Zhang Q, Payungporn S. High-Throughput MicroRNA Profiles of Permissive Madin-Darby Canine Kidney Cell Line Infected with Influenza B Viruses. Viruses 2019, 11(11), 986; https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Fu2790089.ct.sendgrid.net%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbWg-2F9tK-2FvIbqzTuN-2BF8dNv7olAn1jEg5A5z9brFOZbZ6NCP3_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YK-2Bl80FZr8yRojxc9qkUsi1f95-2BbQtSf9Bl6IgP-2BffsM-2BupGL-2Fy6nYJyUym88EwBVS8AFDfSsgpducn-2Fi61c1-2BjOpZ3TGvZp7PiM7SK1ij1VMdVvr44JrJQJxL6JFCYALYdM7mQOXlgEIsXi5FHrU3f-2FydjmmwzEINRL-2B7ZfD-2Bkig-3D-3D&data=05%7C01%7Capprovals%40hra.nhs.uk%7Ce6d7a29d1b42420e64f008dba4f52d0c%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638285145151461062%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=3uD0HZpyspQwq2iC%2BEbX9D6a68d64NkOgtfj1SejD1k%3D&reserved=0
4 Puksuriwong S, Ahmed MS, Sharma R, Krishnan M, Leong S, Lambe T, McNamara PS, Gilbert SC, Zhang Q. MVA-NP+M1 vaccine activates mucosal M1-specific T cell immunity and tissue-resident memory T cells in human nasopharynx-associated lymphoid tissue. J Infect Dis. 2019, https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Fu2790089.ct.sendgrid.net%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbYmQsGrKhqntA-2FbTU5g6kdE1oESb07nD1KlZPJ1zNvbyAcF6_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YK-2Bl80FZr8yRojxc9qkUsi1gwleuoCi2JMOqU-2BJIuFSc1d0GRvJxFFu-2BEUiLKabHLWhyXPfBNjrmuankijqZkj9aJTfgQRq9ogmAOz-2FyducO7OK2iiQNCNTf1JkYyZncyxKPvPHDUpnrEHq2HO3XVUqTqmrhYWHC4ykrhdm5iY8Bg-3D-3D&data=05%7C01%7Capprovals%40hra.nhs.uk%7Ce6d7a29d1b42420e64f008dba4f52d0c%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638285145151461062%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=GMYdRyv2qCO6k7Vl7V7roy8DM2fawEUdmE2r8CkUBZ8%3D&reserved=0 infdis/ jiz593
5 Ascough S, Vlachantoni I, Kalyan M, Haijema B, Wallin-Weber S, Dijkstra-Tiekstra M, Ahmed MS, van Roosmalen M, Grimaldi R, Zhang Q, et al. Local and Systemic Immunity Against RSV Induced by a Novel Intranasal Vaccine: A Randomised, Double- Blind, Placebo-Controlled Trial. Am J Respir Crit Care Med. 2019; 15;200(4):481-492
6 Aljurayyan A, Puksuriwong S, Ahmed M, Sharma R, Krishnan M, Sood S, Davies K, Rajashekar D, Leong S, McNamara PS, Gordon S, Zhang Q. Activation and induction of antigen-specific T follicular helper cells (TFH) play a critical role in LAIV-induced human mucosal anti-influenza antibody response. J Virol. 2018 Mar 21. doi: 10.1128/JVI.00114-18.
7 Kim MY, Copland A, Nayak K, Chandele A, Ahmed MS, Zhang Q et al, Plant-expressed Fc-fusion protein tetravalent dengue vaccine with inherent adjuvant properties. Plant Biotechnol J. 2018; 16 (7). 1283 – 1294.
8 Mahallawi WH., Khabour OF, Zhang Q, Makhdoum HM, Suliman BA, MERS-CoV infection in humans is associated with a pro-inflammatory Th1 and Th17 cytokine profile. Cytokine 2018 Apr;104:8-13. doi: 10.1016/j.cyto.2018.01.025.
9 Mubarak A, Ahmed MS, Upile N, Paton JC, Mitchell T, Cunliffe N, Zhang Q. A dynamic relationship between mucosal Th17 and Treg in nasopharynx evolves with age and appears a critical determinant associated with the clearance of pneumococcal carriage in humans. Clin Microbiol & Infect. 2016;10.1016/j.cmi.2016.05.017
10 Aljurayyan AN, Sharma R, Upile N, Beer H, Vaughan C, Xie C, Achar P, Ahmed MS, McNamara P, Gordon S, Zhang Q. A critical role of T follicular helper cells in human mucosal anti-influenza response that can be enhanced by immunological adjuvant CpG-DNA. Antiviral Research 2016, doi:10.1016/j.antiviral
11 Mullin J, Ahmed MS, Sharma R, Temperton N, McNamara P, Lambe T, Gilbert SC, Zhang Q. Activation of cross-reactive mucosal T and B cell responses in human nasopharynx-associated lymphoid tissue in vitro by Modified Vaccinia Ankara-vectored influenza vaccines. Vaccine 2016; 34(14): 1688-1695
12 Ahmed MS, Jacques LC, Mahallawi W, Ferrara F, Temperton N,, Upile N, Vaughan C, Sharma R, Beer H, Hoschler K, McNamara PS, Zhang Q. Cross-reactive immunity against influenza viruses in children and adults following 2009 pandemic H1N1 infection. Antiviral Research. 2015 Feb;114:106-12.REC name
South East Scotland REC 02
REC reference
14/SS/1058
Date of REC Opinion
25 Sep 2014
REC opinion
Favourable Opinion