COVAB (COVID-19 antibody repertoires in infection and vaccination)

Health

COVAB (COVID-19 antibody repertoires in infection and vaccination)

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, represents a major threat to health. It is recognised that research networks must work together to operate more quickly and obtain results. By studying antibody evolution in the UK and Uganda, we can compare populations. Furthermore , developing an ex vivo challenge model for SARS-CoV-2 will facilitate early vaccine development. In parallel we will carry social science public engagement work to develop strategies to deliver information to communities in a way that people understand and that limits the spread of misinformation.

What is COVAB?

COVAB is a collaborative African / European SARS-CoV-2 programme running in South Africa, Sweden, UK and Uganda.

COVAB Partners

COVAB is a consortium of clinicians, virologists, statisticians, social scientists, immunologists, and public engagement and communicators. The preparatory work was undertaken by King's and the project involves partners from Africa and Europe. The antibody evolution component will be undertaken in the UK and Uganda (UVRI). The ex vivo challenge study will be conducted in Johannesburg, South Africa, with the ex vivo challenge taking place in laboratories based at the WITS/UCT in South Africa, and Imperial College in London. Markers of inflammation will be analysed at WITS, Imperial College and the Karolinska Institute. Antibody levels will be analysed at KCL.

Aims

1. Understanding antibody evolution following exposure to and/or SARS-CoV-2 infection
a. Characterising quality and phenotype of protective antiviral antibodies in COVID-19 patients and healthcare workers in UK and Uganda
b. Investigating COVID-19 antibody evolution and durability (ELISA Ab and nAb responses) in RT-PCR confirmed COVID-19 cases and contacts
c. Determine the impact of previous exposure to seasonal coronavirus infections on protection and severity of SARS-CoV-2 infection.
d. Clone SARS-CoV-2 spike specific human monoclonal antibodies with potent virus neutralising capabilities.

2. Using the mucosal tissue explant model to investigate factors associated with infection by SARS-CoV-2 across oral and nasal mucosa biopsies.
a. Validate ex vivo challenge model for use in SARS-CoV-2 across nasal and oral mucosa
b. Determine whether individuals with past exposure to SARS-CoV-2 can be re-infected
c. Determine whether SARS-CoV-2 acquisition susceptibility is affected by HIV serostatus, age, or inflammation
e. Determine effect of SARS-CoV-2 and prevention agents on upper respiratory tract immunology
We will conduct a prospective ex vivo SARS-CoV-2 challenge study using oral and nasal tissue biopsies taken from 5 groups of healthy volunteers.

3. Develop understanding from communities to develop information tools and engagement for future COVID vaccine trials
Qualitative interviews will be carried out in the General Population cohort, a rural community, Uganda.

Impact

Through evaluating antibody development and cloning novel monoclonal antibodies in COVID-19, we aim to identify a conserved nAb across two countries that could be used for vaccine and immunotherapy. It is the first time that ex vivo challenge has been used for SARS-CoV-2 transmission.

This project is part of the EDCTP2 programme supported by the European Union.

Publications

Harrington, P., de Lavallade, H., Doores, K.J., O’Reilly, A., Seow, J., Graham, C., Lechmere, T., Radia, D., Dillon, R., Shanmugharaj, Y., Espehana, A., Woodley, C., Saunders, J., Curto-Garcia, N., O’Sullivan, J., Raj, K., Kordasti, S., Malim, M.H., Harrison, C.N. and McLornan, D.P. (2021). Single dose of BNT162b2 mRNA vaccine against SARS-CoV-2 induces high frequency of neutralizing antibody and polyfunctional T-cell responses in patients with myeloproliferative neoplasms. Leukaemia 35, 3573-3577.

Rosa, A., Pye, V.E., Graham, C., Muir, L., Seow, J., Ng, K.W., Cook, N.J., Rees-Spear, C., Parker, E., Silva dos Santos, M., Rosados, C., Susana, A., Rhys, H., Nans, A., Masino, L., Roustan, C., Christodoulou, E., Ulferts, R., Wrobel, A.G., Short, C.-E., Fertleman, M., Sanders, R.W., Heaney, J., Spyer, M. Kjaer, S., Riddel, A., Malim, M.H., Beale, R., MacRae, J.I., Taylor, G.P., Nastouli, E., van Gils, M.J., Rosenthal, P.B., Pizzato, M., McClure, M.O., Tedder, R.S., Kassiotis, G., McCoy, L.E., Doores, K.J.and Cherepanov, P. (2021). SARS-CoV-2 can recruit a haem metabolite to evade antibody immunity. Science Advances 7, eabg7607.

Graham, C., Seow, J., Huettner, I., Kahn, H., Kouphou, N., Acors, S., Winstone, H., Pickering, S., Galao, R.P., Dupont, L., Lista, M.J., Jimenez-Guardeño, J.M., Laing, A.G., Wu, Y., Joseph, M., Muir, L., van Gils, M.J., Ng, W.M., Guyvesteyn, H.M.E., Zhao, Y., Bowden, T.A., Shankar-Hari, M., Rosa, A., Cherepanov, P., McCoy, L.E., Hayday, A.C., Neil, S.J.D., Malim, M.H. and Doores, K.J. (2021). Neutralization potency of monoclonal antibodies recognizing dominant and subdominant epitopes on SARC-CoV-2 Spike is impacted by the B.1.1.7 variant. Immunity 54, 1276-1289.

Mahil, S.K., Bechman, K., Raharja, A., Domingo-Vila, C., Baudry, D., Brown, M.A., Cope, A.P., Desandi, T., Graham, C., Lechmere, T., Malim, M.H., Meynell, F., Pollock, E., Seow, J., Sychowska, K., Barker, J.N., Norton, S., Galloway, J.B., Doores, K.J., Tree, T.I.M. and Smith, C.H. (2021). The effect of methotrexate and targeted immunosuppression on humoral and cellular immune responses to the COVID-19 vaccine BNT162b2: a cohort study. Lancet Rheumatology 3, e627-e637.

Dupont, L., Snell, L.B., Graham, C., Seow, J., Merrick, B., Lechmere, T., Maguire, T.J.A., T., Hallett, S.R., Pickering, S., Charalampous, T., Alcolea-Medina, A., Huettner, I., Jimenez-Guardeño, J.M., Acors, S., Almeida, N.,Cox, D., Dickenson, R.E., Galao, R.P., Kouphou, N., Lista, M.J., Ortega-Prieta, A.M.,Wilson, H., Winstone, H., Fairhead, C., Su, J.Z., Nebbia, G., Batra, R., Neil, S., Shankar-Hari, M., Edgeworth, J.D., Malim, M.H. and Doores, K.J. (2021). Neutralizing antibody activity in convalescent sera from infection in humans with SARS-CoV-2 and variants of concern. Nature Microbiology 6, 1433–1442.

Mahil, S.K., Bechman, K., Raharja, A., Domingo-Vila, C., Baudry, D., Brown, M.A., Cope, A.P., Dasandi, T., Graham, C., Khan, H., Lechmere, T., Malim, M.H., Meynell, F., Pollock, E., Sychowska, K., Barker, J.N., Norton, S., Galloway, J.B., Doores, K.J., Tree, T.I.M. and Smith, C.H. (2022). Humoral and cellular immunogenicity to a second dose of COVID-19 vaccine BNT162b2 in people receiving methotrexate or targeted immunosuppression: a longitudinal cohort study. Lancet Rheumatology 4, e42-e52.

Lechmere, T., Snell, L.B., Graham, C., Seow, J., Shalim, Z.A., Charalampous, T., Alcolea-Medina, A., Batra, R., Nebbia, G., Edgeworth, J.D., Malim, M.H. and Doores, K.J. (2022). Broad neutralization of SARS-CoV-2 variants, including omicron, following breakthrough infection with delta in COVID-19 vaccinated individuals. mBio 13, e03798-21.

Seow, J., Graham, C., Hallett, S.R., Lechmere, T., Maguire, T.J.A., Huettner, I., Cox, D., Khan H., Pickering, S., Waters, A., Ward, C.C., Mant, C., Pitcher, M.J., Spencer, J., Fox, J., Malim, M.H. and Doores, K.J. (2022). ChAdOx1 nCoV-19 (AZD1222) vaccine elicits monoclonal antibodies with potent cross-neutralizing activity against SARS-CoV-2 viral variants. Cell Reports 39, 110757.

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