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Gupta Lab, Cambridge Profile picture
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11 Mar, 4 tweets, 2 min read
Sharing our analysis of neutralising antibody responses following Pfizer vaccine and convalescent plasma against B.1.1.7+/- E484K Spike pseudotyped virus. Big thank you to the team that made this possible @CUH_NHS @CambridgeBRC @OH_wellbeing @RealMcCoyLab nature.com/articles/s4158…
Antibody levels were much higher after the second dose as expected. Following the first dose, three times more serum was needed to block B.1.1.7 and following second dose around two fold more. This small change is only likely to be relevant in those with low antibody levels.
We also noted that B.1.1.7 viruses with E484K were transmitting in the UK. We tested vaccine and convalescent sera against B.1.1.7 Spike bearing pseudoviruses +/-E484K. There was a larger drop in neutralisation against B.1.1.7 E484K (vaccine sera 6x; convalescent sera 11x).
Take home: vaccines should be effective against B.1.1.7 in general, but we don't know about those with suboptimal immune responses. Transmission of variants with E484K on background of B.1.1.7 (and others) is a reality and may not be controlled. Modified vaccines are on the way.

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More from @GuptaR_lab

Gupta Lab, Cambridge Profile picture
29 Jan
Following on from the first dose Pfizer data below where 7/15 participants above the age of 80 did not achieve neutralisation of virus, we report that all 15 have achieved neutralisation 3 weeks after second dose.
It could be that >80 yo are slower in mounting responses but this is unlikely and also leaves people vulnerable despite vaccine. Remember >80 y o are not featuring in trials so they might still get severe disease. Pre print to come but significant delays.
We should add that the second dose was given at 3 weeks after the first. Likely we should stick to this schedule in those above 80 years. Huge effort from @damicollier @rpdatir @CambridgeBRC
Read 5 tweets
Gupta Lab, Cambridge Profile picture
15 Jan
Sharing some real world data on antibody responses to the Pfizer mRNA vaccine. We tested serum from 23 participants (median age 82) vaccinated with the first dose 3 weeks previously.
Serum IgG antibodies against Spike were measured with a luminex assay. Virus neutralisation by participant serum was measured with a virus pseudotyping system where virus particles are made that express the SARS-CoV-2 Spike protein. The figure shows that the two were correlated.
All participants under 80 (n=8) demonstrated reasonable neutralisation titres against wild type virus (D614G). However, 7/15 of those above 80 failed to neutralise virus to 50%. In blue and purple are participants who neutralised virus. In grey is a participant that did not.
Read 6 tweets
Gupta Lab, Cambridge Profile picture
30 Dec 20
B1.1.7 has more than 20 changes in genetic code, of which 8 are in the Spike protein (shown below). Spike is the target of many of our immune and vaccine responses. These changes can alter the shape of the spike, and that is why scientists are worried about viruses like this.
The numbers infected with B1.1.7 has been growing faster than other UK variants based on independent data sources. This variant of SARS-CoV-2 is therefore thought to be more transmissible by around 50%. Data suggest it does not lead to more severe illness however.
The N501Y mutation is in an important area called the receptor binding domain that interacts with our cells directly. N501Y has been reported to increase binding, though could play a role in avoiding antibodies. This mutation has formed clusters in a number of countries.
Read 6 tweets
Gupta Lab, Cambridge Profile picture
11 Dec 20
The first evidence of in vivo SARS-CoV-2 escape from antibodies: emergent Spike deletion H69/V70 and D796H mutation in a convalescent plasma (CP) treated patient. These mutations conferred reduced susceptibility to the CP and sera from multiple donors. medrxiv.org/content/10.110…
Clinical case summary. Individual with lymphoma treated with B cell depletion therapy (rituximab). Image
Phylogenetic analysis of published cases demonstrates diversity of SARS-COV-2 virus in long term shedders. This case is in green. ImageImage
Read 8 tweets

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