Tweet

Tulio de Oliveira

29 Mar, 14 tweets, 6 min read

@nature

Today paper on neutralization of 501Y.V2 (B.1.351) - Show effective neutralization of other SARS-CoV-2 lineages by 501Y.V2 @nature

nature.com/articles/s4158…

All start with a good cohort... We obtained convalescent plasma & sequenced the matching infecting virus of 1st & 2nd wave

A first wave variant lacking the 501Y.V2 RBD and NTD mutations (B.1.1.177) was outgrown from one participant infected in the first South African infection wave, and 501Y.V2 was outgrown from a participant at the beginning of the second wave.

A focus forming live virus neutralization assay (LVNA) was used to quantify neutralization.

We used convalescent plasma from many lineages to neutralize the virus outgrown. Variants which elicited the antibody immunity in the plasma samples are highlighted in green boxes. Variants which were outgrown are highlighted in magenta boxes.

A representative focus forming assay using plasma from first wave infected participant 039-13- 0015 (B) or 501Y.V2 infected participant 039-02-0033 (C). Columns are plasma dilutions, ranging from 1:25 to 1:1600, a plasma pool from 3 uninfected individuals and a no plasma control.

Quantified neutralization of B.1.177 virus (1st wave infection) per participant. Left panel Antibody control, right panel plasma neutralization of 1st Wave, 501Y.V2 and a virus (B.1.1.56) containing extra E484K .

Right plot is neutralization of the 501Y.V2 by A02051 (PRNT50 = 3.5 ng/mL (2.9–4.1 ng/mL)) and uninfected plasma. Left plot is neutralization of 501Y.V2 virus by plasma from convalescent participants (Now different from 1st wave).

Summary results show 1st wave plasma does not neutralize well 501Y.V2 (B.1.351) - 3.2 to 41.9 reduction. But that the opposite is not true, small fold change of 510Y.V2 to first wave (B.1.177) 1.6 - 7.2 reduction. Interesting the 1st wave with E484K neutralize both viruses (n=1).

Cross-neutralization of first infection wave and 501Y.V2 virus across all participants. Left plot shows neutralization of first wave virus, right plot shows neutralization of 501Y.V2. Sigmoidal fits were performed to the means of 1st (orange points) and 501Y.V2 (blue points)

Conclusions:

A) In cross- neutralization, 501Y.V2 virus was poorly neutralized by first wave plasma, with a 15.1-fold drop relative to 501Y.V2 neutralization by second wave plasma across participants.

B) In contrast, 501Y.V2 plasma cross-neutralization of 1st wave virus was more effective, showing only a 2.3-fold decline relative to 1st wave plasma neutralization of 1st wave virus. While we only tested one plasma elicited by E484K alone, this potently neutralized both variants

C) The observed effective neutralization of first wave virus by 501Y.V2 infection elicited plasma provides preliminary evidence that vaccines based on VOC sequences could retain activity against other circulating SARS-CoV-2 lineages.

@sigallab

Thanks a fantastic team in South Africa for this great science !!!! @sigallab @krisp_news @houzhou @rjlessells @EduanWilkinson @Sandile_Cele22 @AHRI_News

Open & Freely Available manuscript published today in Nature:

nature.com/articles/s4158…

• • •

Missing some Tweet in this thread? You can try to force a refresh

This Thread may be Removed Anytime!

Twitter may remove this content at anytime! Save it as PDF for later use!

More from @Tuliodna

Tulio de Oliveira

@Tuliodna

25 Mar

We just submitted a pre-print 'A novel variant of interest (VOI) of SARS-CoV-2 with multiple spike mutations detected through travel surveillance in Africa.'

This VOI has 31 amino acids mutations. In Spike has 11 mutations and three deletions in the N-terminal domain

@jbloom_lab

It has some key mutations, including the E484K, R346K and P681H. The R346K is the associated with resistance to class 3 RBD NAbs recently described by @jbloom_lab
There are also 5 substitutions and 3 deletions in the NTD antigenic supersite (Y144Δ, R246M, SYL247-249Δ and W258L)

It the most diverse A lineage sequencers ever described. It also worry us as it was found in three travelers from Tanzania in Angola. There is almost no data from COVID-19 in Tanzania.

Read 8 tweets

Tulio de Oliveira

@Tuliodna

9 Mar

@rjlessells

Finally out! Emergence of a SARS-CoV-2 variant of concern with mutations in spike glycoprotein disq.us/t/3vewz4s

So many people to thank, thank you and thank you! @rjlessells @houzhou @Mittenavoig @MRCza @dsigovza

Great to see South African science advancing fast!

The paper starts by showing how the second wave in South Africa arise so quickly, which was completely unexpected as we were in the start of our summer.

It show how a new and unusual cluster emerged among the dozens of different lineages already circulating in South Africa.

Read 10 tweets

Tulio de Oliveira

@Tuliodna

7 Mar

A truly global collaboration between groups in South Africa, U.K., Belgium, Sweeden, USA to understand convergent evolution of the variants of concern.

medrxiv.org/content/10.110…

ARS-CoV-2 genome map indicating the locations and encoded amino acid changes of what we considered here to be signature mutations of 501Y.V1 (B.1.1.7), 501Y.V2 (B.1.251) and 501Y.V3 (p1) sequences. Amazing how different and similar the variants are...

Signals of positive selection detected at 37 signature mutation sites in the VOCs between March 2020 and January 2021. In short, must of the sites in Spike are in convergent evolution, including 501, 484, 417, 18, etc.

Read 6 tweets

Tulio de Oliveira

@Tuliodna

7 Mar

Another knock down paper from South Africa! This time 501Y.V2 (B.1.351) is giving again good news with confirming that neutralise other lineages but also another VOC, the P1.

SARS-CoV-2 501Y.V2 (B.1.351) elicits cross-reactive neutralizing antibodies biorxiv.org/content/10.110…

We observed no significant difference in the magnitude of binding (Figure 1A) or neutralizing (Figure 1B) responses between the 501Y.V2 cohort and the wave 1 (i.e. B.1 original lineages) admission samples.