Thread by @Williams_T_C

what a difference a month makes in a pandemic

Dec '20: lab studies show potential for SARS-CoV-2 mutations to impact antibody neutralisation

Jan '21: clinical trials @Novavax & @JNJGlobalHealth show 501Y.V2 appears to impact vaccine effectiveness, confirming predictions 🧵1/n

interested in the science underlying this?

if so my Comment with Wendy Burgers @virusmonologues is out today @LancetRespirMed thelancet.com/journals/lanre…

thankyou to @jbloom_lab for insightful comments on the piece 2/n

first important message is to highlight we are in incredibly fortunate position with SARS-CoV-2 vaccines

multiplicity of approaches to choose from (mRNA, Spike protein, adenovirus vector)

all of which show efficacy >50% even with the 501Y.V2 variant virological.org/t/mutations-ar… 3/n

most of these vaccines could be reformulated in as little as 6 weeks

and it is likely that regulators will find a way to fast-track the approval of these reformulations 4/n

second important message is that the overall effectiveness of immunisation will correlate with rates of vaccine uptake

we have a responsibility as health-care providers, researchers and policy makers to act as advocates for immunisation #VaccinesWork @JeremyFarrar @WHO 5/n

and to advise individuals with questions about vaccines to seek this information from reliable sources

the higher the proportion of a population vaccinated, the lower the number of susceptible individuals, and the fewer opportunities SARS-CoV-2 has to spread and mutate 6/n

our Comment highlights how unusual SARS-CoV-2 appears to be in its evasion of the human immune response

we outline previous viral vaccines and how they all (with the exception of influenza, with its regular recombination events) 7/n

appear to have been fairly robust in terms of dealing with mutations in the virus being vaccinated against

(important to highlight though that there are only a relatively small number of recombinant viral vaccines out there) 8/n

whether this evasion is due to a drift or selection is a gnarly question, particularly whether vaccines themselves could drive selection @arambaut @firefoxx66 @dkenned11 9/n

we examine laboratory studies for SARS-CoV-2 and other viruses that demonstrate the vulnerability of monoclonal antibodies to one or two point mutations in the virus 10/n

and outline how lab studies also show that the limited polyclonal response to Spike appears to also render the human humoral immune response vulnerable to viral genetic variability doi.org/10.1101/2020.1… 11/n

more recent studies show that convalescent sera after infection with the original D614G variant provides sub-optimal protection to the 501Y.V2 variant biorxiv.org/content/10.110…

and studies of sera from vaccinated individuals show the same effect, to to a lesser degree 12/n

the clinical equivalent of a laboratory experiment is the randomised controlled trial

these studies from @Novavax ir.novavax.com/news-releases/… & @JNJGlobalHealth jnj.com/johnson-johnso… seem to confirm the predictions made in the lab 13/n

reassuring features from these trials are the ongoing protection against severe disease

could this be due in part to T cell activity, where a broader range of epitopes are known to be recognised? science.sciencemag.org/content/370/65… 14/n

the real learning point for everyone is that we've had to challenge our preconceptions about RNA viruses:

although the mutation rate in SARS-CoV-2 is low, this seems to be accelerated in certain contexts, and a small number of mutations can have a dramatic phenotypic effect 15/n

SARS-CoV-2 is much more transmissible than other enveloped RNA respiratory viruses, as evidenced by the absence of influenza and RSV so far this winter in the Northern Hemisphere 16/n

we underestimate this virus at our peril

the best way to ensure the effectiveness of the vaccines that we already have is to work quickly to drive down the circulation of SARS-CoV-2

and to act decisively, collaboratively, and globally

#ZeroCovid

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