Thread by @CillianDeGascun

An introductory thread on B.1.617.2 and why we’re concerned about vaccine effectiveness (VE) against this virus. TL:DR The vaccines will work against B.1.617.2 but two doses of vaccine will be required to optimise effectiveness 1/n

The primary way of measuring likely VE (or more specifically antibody effectiveness) against a virus in the lab is the neutralisation test. In this test, we try to grow (or culture) the virus in the presence of antibodies in the laboratory 2/n

If the antibody is effective, we won’t see any growth because the virus has been ‘neutralised’. If the antibody is not effective, then we will see growth. However, it’s not a yes/no answer. There will be a range of growth from none to lots 3/n

The amount of growth depends on how much antibody is present in the sample we're studying, and what dilution of the sample is used. The study samples – containing antibody – that we use for VE studies typically come in three different types 4/n

These are monoclonal antibodies; blood samples (usually serum) from people who have recovered from infection (convalescent serum); and blood samples from vaccinated individuals (vaccinee serum) 5/n

Most of these study samples will neutralise the virus in their undiluted (neat) form. However, that doesn’t tell us much & doesn’t allow us to compare how effective these study samples (or the antibodies they contain) are against different viruses 6/n

For that reason, we dilute the samples (usually 1 in 2; 1 in 4; 1 in 8; 1 in 16 etc.) By doing this, we can identify the exact dilution of a particular study sample required to neutralise a given virus. That dilution is called the neutralisation titre for the virus 7/n

If the virus is very sensitive (or susceptible) to the antibodies we’re studying, then the neutralisation titre will be high. This means that we can dilute the sample a lot e.g. 1 in 256 or 1 in 512, and it is still capable of neutralising the virus 8/n

If the virus is less susceptible (or more resistant) to the antibodies we’re studying, then the neutralisation titre will be lower. This means that we can only dilute the sample a couple of times e.g. 1 in 4 or 1 in 8, before it loses the ability to neutralise the virus 9/n

In its #VOC Technical Briefing @PHE_UK has reported reductions in neutralising activity for B.1.617.2 across multiple sera in different labs, including: convalescent sera & vaccinee sera against live virus; and vaccinee sera against a B.1.617.2 pseudovirus 10/n

This in itself is concerning. However, it’s important to remember that the virus can still be neutralised, but it’s more difficult to neutralise than B.1.1.7 (variant first reported in UK) for example. The question is what impact this difference will have in the real world 11/n

Part of the problem is that we don’t know the required neutralising antibody (NAb) threshold for protection against B.1.617.2. However, people who produce a lot of NAbs post-vaccine are likely to be protected; conversely, people who don’t produce a lot of NAbs might not 12/n

The reduced neutralising activity seen with vaccinee sera against B.1.617.2 helps to explain the significant reduction in vaccine effectiveness of a first dose of a #SARSCoV2 vaccine, against symptomatic disease, reported by @PHE_UK. What’s reassuring 13/n

is the more modest (albeit still significant) reduction seen after 2 doses. Reduced VE with increased transmissibility could mean a review of the population vaccination threshold required for community level protection If B.1.617.2 becomes dominant in Ireland 14/n

In summary, the concern for us in #Ireland is the combination of: a more transmissible virus; a large proportion of the population not fully vaccinated; and the increase in social contacts associated with the easing of restrictions 15/n

However, thanks to @HSELive, @HSEImm, @hpscireland, and our own individual behaviour, we can control this virus until the majority of the population is fully vaccinated, so please #StaySafe and #GetYourShot #SARSCoV2 #VaccinesWork #VaccinesForAll 16/n

PS: I didn’t mention cellular immunity in this thread, in part because I’m not an immunologist, but the data on the effectiveness of the cellular immune response are also very reassuring in the context of all #SARSCoV2 #Variants of concern described to date 17/17