Last updated on 15/09/2020

Alpacas and COVID-19.

The Coronavirus family of viruses causes a wide range of illnesses in animals. These range from the common cold to Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS) in humans but can also cause diarrhoea, hepatitis, encephalomyelitis and respiratory illnesses in other species. A coronavirus infection causing diarrhoea in young camelid crias has also been identified [28 and 29]. These viruses can be transmitted between animals and people, a process known as zoonosis, so it is significant that wildlife can act as reservoirs of coronaviruses [31 and 32]. SARS-CoV-2, more widely known as COVID-19, is also a member of the Coronavirus group.
One result of virus infection is the production of antibodies by plasma B cells. Antibodies are immune system proteins responsible for neutralising the viruses by binding to them and preventing them from infecting further cells. Most mammals produce only one form of antibody that is made from a combination of heavy and light protein chains. These form a 'Y'-shaped structure with the heavy chain proteins forming the backbone of the entire 'Y' and the light-chain proteins lining the arms of the 'Y'. It is the top of the 'Y'-shape that contains a region which tightly and specifically binds to an area on the antigen. Variations in this region allow for specific binding to a vast range of different structures. Camelids differ, as in addition to the antibody described, they also possess a smaller variant (around 40% of the total) known as a single domain antibody [27]. This antibody form still has the ‘Y’ structure though the arms are shorter due to the absence of light-chain proteins but the variable region are still located along the arms. Separation and isolation of the arms from the stem yields the nanobody.
A critical element of the COVID-19 infection process is binding of the viral ‘spike’ glycoprotein to the cell receptor protein (angiotensin-converting enzyme 2 (ACE2)), a process that allows the virus particle to be taken into the cell. The nanobody strongly binds to the COVID-19 virus’ spike proteins [33] thus preventing binding to the receptor and blocking entry. Synchrotrons are being used to determine the structure of nanobodies bound to the spike protein of SARS-CoV-2 and determine the exact target area of the antigen.
The nanobodies are obtained by immunising an alpaca or llama with specific fragments of the virus' spike protein. After a number of days, blood is taken from the alpaca and the antibodies extracted. Their small size, solubility and stability make them attractive as candidate therapeutic agents. These properties give them the potential to be used similarly to a convalescent serum, effectively stopping progression of the disease and also developed into an inhaled treatment since the antibodies would be deposited directly into the lungs, the primary location of COVID-19 infection.
Given the severity of the COVID-19 pandemic and the urgent need for innovative therapeutic solutions, there are several international scientific groups now researching this area using both alpacas and llamas as the source of nanobodies.

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References.

Most of the literature below can be accessed by clicking on the highlighted link. Some links will access the appropriate web page from which the article can be downloaded but others will immediately start downloading the full reference.

27. Hamers-Casterman, C., Atarhouch, T., Muyldermans, S., Robinson, G., Hamers, C.,Songa, E.B., Bendahman, N., Hamers, R., (1993). Naturally occurring antibodies devoid of light chains. Nature, 363: 446–448.

28. Cebra, C.K., Mattson, D.E., Baker, R.J., Sonn, R.J., Dearing, P.L. (2003). Potential pathogens in feces from unweaned llamas and alpacas with diarrhea. J. Am. Vet. Med. Assoc. 223(12): 1806–1808.

29. Jin, L, Cebra, C.K., Baker, R.J., Mattson, D.E., Cohen, S.A., Alvarado, D.E. and Rohrmann, G.F. (2007). Analysis of the genome sequence of an alpaca coronavirus. Virol., 365(1): 198-203.

30. Vanlandschoot, P., Stortelers, C., Beirnaert, E., Ibañez, L.I., Schepens, B., Depla, E., Saelens, X. (2011). Nanobodies: new ammunition to battle viruses. Antivir. Res., 92: 389-407.

31. Poon, L.L.M., Chu, D.K.W., Chan, K.H., Wong, O.K., Ellis, T.M., Leung, Y.H.C., Lau, S.K.P., Woo, P.C.Y., Suen, K.Y., Yuen, K.Y., Guan, Y. and Peiris, J.S.M. (2005). Identification of a Novel Coronavirus in Bats. J. Virol., 79(4): 2001–2009.

32. Lam, T.T., Jia, N., Zhang, Y. et al. (2020). Identifying SARS-CoV-2-related coronaviruses in Malayan pangolins. Nature, 583: 282–285. https://doi.org/10.1038/s41586-020-2169-0

33. Hanke, L., Perez, L.V., Sheward, D.J., Das, H., Schulte, T., Moliner-Morro, A., Corcoran, M., Achour, A., Karlsson Hedestam, G.B. Hällberg, B.M., Murrell, B. and McInerney, G.M. (2020). An alpaca nanobody neutralizes SARS-CoV-2 by blocking receptor interaction. Posted 8th July 2020. doi: https://doi.org/10.1101/2020.06.02.130161

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