Investigation of mucosal immune responses to respiratory pathogens including SARS-CoV-2 and influenza viruses and related vaccines

COVID-19 pandemic caused by SARS-CoV-2 virus infection has resulted in significant morbidity and mortality. Despite the current vaccination that reduces the numbers of severe COVID-19 cases and death, it fails to prevent new infections in many people which still result in high numbers of hospitalisation. One of the main reasons for the failure of current vaccines (administered intramuscularly) to effectively prevent infection is thought due to the lack of ability to induce local mucosal immunity, as the injected vaccines produce antibodies mainly in the blood, few of which make it to the nasopharynx (upper airway) where the initial infection takes place. Understanding natural infection- and vaccine-induced mucosal immunity to SARS-CoV-2 in human nasopharynx will provide valuable information(1, 2) for developing more effective vaccination strategy (e.g. intranasal vaccines) against new infection. In addition, with the high prevalence of SARS-CoV-2 in the population, there is likely substantial interactions between SARS-CoV-2 and other common pathogens such as influenza virus in the nasopharynx. It will be important to understand the impact of COVID-19 on immunity to other common pathogens. Adenoids and tonsils are nasopharynx-associated lymphoid tissues (NALT) in human nasopharynx, important for producing local immunity against airway infection. Intranasal vaccines rely on NALT to produce immunity against infection. Dr Zhang’s group established an ex vivo cell culture system to study the T and B cell immunity to respiratory pathogens and vaccines(3-10). The use of this in vitro culture system will have a great impact on the understanding of human immunity against infection and the development of new vaccines.

With the use of state-of-the-art facilities, we will study the immune responses (e.g. T & B cell immunity, cytokine and antibody responses) in human NALT tissue to SARS-CoV-2 and influenza, and novel vaccines (e.g. intranasal vaccines) in individuals with or without prior COVID-19 infection or vaccination. The information will be invaluable for developing new and more effective vaccines.

Applicants are expected to hold a good honours degree (first or upper second) in biological science, preferably with Immunology. Enthusiasm for, and commitment to, independent study is essential.

Open to UK applicants only.

You'll have access to state-of-the-art facilities include cell culture,   multi-colour flowcytometry, fluorescence microscopy, immunoassays, RT-PCR, scRNA sequencing, B cell receptor repertoire analysis etc.

References

1.             Matuchansky C. 2021. Mucosal immunity to SARS-CoV-2: a clinically relevant key to deciphering natural and vaccine-induced defences. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases 27:1724-1726.

2.             Russell MW, Moldoveanu Z, Ogra PL, Mestecky J. 2020. Mucosal Immunity in COVID-19: A Neglected but Critical Aspect of SARS-CoV-2 Infection. Frontiers in Immunology 11.

3.             Lu YJ, Gross J, Bogaert D, Finn A, Bagrade L, Zhang Q, Kolls JK, Srivastava A, Lundgren A, Forte S, Thompson CM, Harney KF, Anderson PW, Lipsitch M, Malley R, Lu YJ, Gross J, Bogaert D, Finn A, Bagrade L, Zhang Q, Kolls JK, Srivastava A, Lundgren A, Forte S, Thompson CM, Harney KF, Anderson PW, Lipsitch M, Malley R. 2008. Interleukin-17A mediates acquired immunity to pneumococcal colonization. PLoS Pathogens 4:e1000159.

4.             Gray C, Ahmed MS, Mubarak A, Kasbekar AV, Derbyshire S, McCormick MS, Mughal MK, McNamara PS, Mitchell T, Zhang Q. 2014. Activation of memory Th17 cells by domain 4 pneumolysin in human nasopharynx-associated lymphoid tissue and its association with pneumococcal carriage. Mucosal Immunol 7:705-717.

5.             Zhang Q, Leong SC, McNamara PS, Mubarak A, Malley R, Finn A. 2011. Characterisation of Regulatory T Cells in Nasal Associated Lymphoid Tissue in Children: Relationships with Pneumococcal Colonization. PLoS Pathog 7:e1002175.

6.             Mahallawi WH, Kasbekar AV, McCormick MS, Hoschler K, Temperton N, Leong SC, Beer H, Ferrara F, McNamara PS, Zhang Q. 2013. Infection with 2009 H1N1 Influenza Virus Primes for Immunological Memory in Human Nose-Associated Lymphoid Tissue, Offering Cross-Reactive Immunity to H1N1 and Avian H5N1 Viruses. Journal of Virology 87:5331-5339.

7.             Mullin J, Ahmed MS, Sharma R, Upile N, Beer H, Achar P, Puksuriwong S, Ferrara F, Temperton N, McNamara P, Lambe T, Gilbert SC, Zhang Q. 2016. 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 34:1688-1695.

8.             Puksuriwong S, Ahmed MS, Sharma R, Krishnan M, Leong S, Lambe T, McNamara PS, Gilbert SC, Zhang Q. 2019. Modified Vaccinia Ankara–Vectored Vaccine Expressing Nucleoprotein and Matrix Protein 1 (M1) Activates Mucosal M1-Specific T-Cell Immunity and Tissue-Resident Memory T Cells in Human Nasopharynx-Associated Lymphoid Tissue. The Journal of Infectious Diseases doi:10.1093/infdis/jiz593.

9.             Zhang Q, Bagrade L, Clarke E, Paton JC, Nunez DA, Finn A, Zhang Q, Bagrade L, Clarke E, Paton JC, Nunez DA, Finn A. 2010. Bacterial lipoproteins differentially regulate human primary and memory CD4+ T and B cell responses to pneumococcal protein antigens through Toll-like receptor 2. Journal of Infectious Diseases 201:1753-1763.

10.           Xu R, Shears RK, Sharma R, Krishna M, Webb C, Ali R, Wei X, Kadioglu A, Zhang Q. 2020. IL-35 is critical in suppressing superantigenic Staphylococcus aureus-driven inflammatory Th17 responses in human nasopharynx-associated lymphoid tissue. Mucosal Immunology doi:10.1038/s41385-019-0246-1.

Dr Qibo Zhang is Senior Lecturer in Immunology in the School of Bioscience and Medicine at University of Surrey. His main research interest has focused on human immunology, and mucosal immunity in particular, to respiratory pathogens and vaccines. His research also covers immune regulation of infection and inflammation/autoimmunity. Current studies include mucosal Immunity to some key human pathogens including influenza, RSV, SARS-CoV-2, S. pneumoniae and S. aureus. Dr Zhang’s research is primarily based on the use of an ex vivo human immune tissue/cell culture system for pathogen/antigen-specific T & B cell immunity and vaccine studies. The unique in vitro system has been used to evaluate many new vaccines & antigens and immuno-regulatory therapeutics in humans, which highlights the translational nature of the research work, utilising basic science to inform novel vaccination and therapeutic strategies. His research has been funded by MRC, NIHR, NC3R, Action Medical Research, SPARKS etc. He has published over 70 peer-reviewed international journal papers, and successfully supervised over 20 PhD students as primary supervisor. He has collaborated extensively with academic colleagues and industry partners (pharmaceutical & vaccine companies).

The PhD students would be based in the Immunology Section alongside other PhD students working on a wide range of topics in immunology.