February 10, 2022

expert reaction to conference abstract looking at antibodies and performance of antibodies after COVID-19 infection versus after vaccination

A conference abstract presented at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) Annual Meeting looks at long-term humoral immunity of individuals after COVID-19 infection and after Pfizer vaccination.

Dr Julian Tang, Honorary Associate Professor/Clinical Virologist, Respiratory Sciences, University of Leicester, said:

“Antibody avidity is a measure of how well an antibody (Ab) binds to its target antigen (Ab) – and this binding strength increases over time as the Ab matures – we can measure this with so called ‘denaturing’ serological assays in the lab.

“The apparent lack of vaccine-induced Ab maturation in this study seems surprising – to me this finding does not make any sense: any antibody response induced by a foreign antigen should rise in avidity over time.  If this is not the case with mRNA vaccine-induced antibodies, this seems odd as they still code for the viral S antigen.

“More traditional subunit or recombinant protein vaccines, like influenza and hepatitis B vaccines, for example, do show an increase in vaccine-induced Ab avidity over time: https://nn.neurology.org/content/1/3/e28; https://www.nature.com/articles/s41541-021-00337-0.

“Finally the correlation with obesity seems slightly odd – given that we know that obesity is a risk factor for more severe COVID-19 – but we also see higher Ab levels in more severe COVID-19 cases, and more aggressive host immune responses can lead to more severe COVID-19.

“As there are so many potential confounders in these findings, we really need to compare the serological outcomes in a larger study across multiple ethnicities (BAME) and socio-economic groups in obese/non-obese individuals with differing levels of COVID-19 clinical severity from multiple COVID-19 vaccines only vs. natural infection only vs. a combination of the two – with appropriate control groups to understand this better.

“Also these avidity assays are not universally standardised – so different labs using their own avidity assays may see different results.

“But generally, natural infection generates a broader and longer-lasting set of immune responses to all the viral antigens – so this is not really surprising.  After all, our immune systems have evolved over several million years to deal with all types of pathogens – so I would expect natural immunity to outperform any vaccine-induced immunity over the longer term.”

Prof Daniel Altmann, Professor of Immunology, Department of Immunology and Inflammation, Imperial College London, said:

“This is a study that impinges on some of the difficult unknowns we’re all grappling with in human immunology studies at this stage in the pandemic.  We now have a very heterogenous global population to understand: never infected/never vaccinated, vaccinated with 1-4 doses of diverse vaccines, different combinations of hybrid immunity from infection plus vaccination, and then, infected only across either the original Wuhan Hu-1 strain, or repeat exposures to any of alpha, beta, gamma, delta, or omicron.  A really complex set of variables to decode!  To do that decoding, you really need quite a granular analysis, across breakthrough infection datasets correlated to detailed analysis of immune repertoire and virus neutralisation.  While the view from other studies is of a better quality of response as assessed by B cell receptor breadth and affinity maturation through vaccination, this study, conversely, reports something described as improved antibody numbers through immunity after infection.  Definitely a work in progress with consensus needed and more to be done.  In terms of consensus on the quality, quantity and durability of protective immunity following spike exposure through infection, vaccination, or hybrid exposure, the jury is still out. ”

Dr Richard Tedder, member of the Clinical Virology Network, said:

“Dr Cohen and colleagues provide an interesting insight into long term follow up of patients following recovery from coronavirus infection as part of a wide ranging longitudinal study.  It is well put together and includes commentary on the decay of antibody.  They indicate that the avidity of antibody post recovery continues to rise in the recovery patient but declines in the immunised vaccine recipient over time.  This observation of high avidity, i.e. the strength with which antibody binds to the virus, which they describe in the recovered patient, is contrary to what we see.  This may reflect different methodology.  Our view from other research which we have conducted is that the post recovery antibody (i.e. in people who have been infected but not received vaccine) is of remarkably low avidity for interacting with viral receptor binding domain, the viral protein which reacts with the target human cell, in spite of there being copious amounts of the antibody in the blood.  This explains why reinfection, usually with mild symptoms, is common.”

Abstract title: ‘Long-term humoral immunity of COVID-19 recovered and BNT162b2 vaccinated individuals: a prospective comparative study’ by C. Cohen et al. was presented at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) Annual Meeting in Lisbon in April. This was under embargo until 23:01 UK time on Thursday 10 February 2022.

This work is not peer-reviewed and there is no paper.

Declared interests

Dr Richard Tedder: “I see no conflict of interest but remind you that we hold patents on three diagnostic components relating to SARS CoV 2.”

None others received.