Correspondence re Covid Update Dr Neil Snowise; Professor Charles Bangham

Questions from Dr Neil Snowise to Professor Charles Bangham regarding his Article on pages 12-14

Dr Neil Snowise

(Corpus Christi College 1974)

Professor Charles Bangham

(Lincoln College, 1977)

NGS: I very much enjoyed Charles Bangham’s excellent article and raised two queries: “Several of these emerging viruses have emerged from bats, as well as the SARS and COVID viruses: it is a curious and interesting feature of bats that they harbour a large number of viruses.” I am aware that bats harbour many viruses but do not get unwell, do we understand why this happens and can we learn anything about their immune system that may help humans?

CB Response: It seems to be generally true that bats harbour a lot of viruses, and that many of them are asymptomatic. There is good evidence that bats have a high constitutive level of expression of Type 1 interferons, which accounts for part of this protection. However, it is not the case that they are completely protected against all viruses: many of them do in fact get sick from the viruses. We also harbour several viruses that persist lifelong, in most cases not causing any disease. The classic examples are the herpesviruses, including HSV1 and 2, VZV, HHV6, and EBV: most of us get infected and never know about it, but an unlucky minority get severe or even fatal diseases, such as the bewildering array of conditions caused by EBV – infectious mononucleosis, Burkitt’s lymphoma, nasopharyngeal carcinoma, and (very recent evidence, from an excellent study published in 2022) multiple sclerosis.

Why bats evolved like this is not yet clear. My own view is that, because they are more mobile than other mammals, they might come into contact with a broader range of pathogens than other species, and so there is a strong selection pressure to evolve a strong first-line (innate) immune response to viruses. But of course, like many evolutionary explanations, this might just be what I often refer to as an ‘evolutionary Just So story’, after Kipling.

NGS: You mention antibodies and T cell memory. We tend to only measure antibodies as a sort of surrogate marker for vaccine efficacy. But T cell memory could be very important. How do we assess this or do we just rely on it, to produce rapid antibodies if re challenged, so actually we cannot assess T cell memory?

CB Response: I did my PhD and then spent most of my research career on the T cell response to viruses, so I am delighted that you bring them up. The importance of a rounded immune response to viruses, that is, one that consists of both antibodies, helper T cells and cytotoxic T cells is something I frequently mention. The helper T cells are of course essential for the antibody response and for the memory immune response – both B cell (antibody) memory and T cell (helper & cytotoxic) memory. Another key point is that there is an enormous and quite disproportionate emphasis on neutralizing antibody (nAb) in antiviral protection. But while nAbs are useful and important, they are not the whole antibody story: antibodies kill viruses by several different mechanisms, including complement fixation and antibody-dependent, cellmediated cytotoxicity (ADCC), both of which depend on the Fc part of the antibody, and neither of which is measured by the standard in vitro assays of virus neutralization by antibody. Neutralization assays are quick, simple, and appealing (‘virus neutralization’ sounds good).

T cell memory can indeed be assayed (we have done countless experiments on this), but because the assays are more difficult technically, longer, and harder to standardize between labs, T cell assays are almost never used routinely as correlates of protection: only in research work.

Overall, antibodies (often nAbs) are measured as a surrogate or correlate of protection, but actual protection requires a lot more.

“it is a curious and interesting feature of bats that they harbour a large number of viruses

Erratum:

Oxford Medicine Autumn/Winter 2021: 100 Years of Insulin – A lifesaving drug and murder weapon by Dr Neil Snowise

The first paragraph on page 18 explains that pro-insulin is cleaved into insulin and C-peptide. A typo stated that “a low insulin:C-peptide ratio can provide invaluable evidence of exogenous insulin administration. This should have read a “high insulin:C-peptide ratio etc.” Thanks to Dr Derek Hockaday for spotting this error. Derek Hockaday

LINK TO ARTICLE: https://issuu.com/oxfordmedicalalumninewsletter/docs/oxford_medicine_autumn_2021

(Brasenose College, 1947)