12 May 2021 Episode 139 : The Indian variant B.1.617: genetics, pathogenicity and sensitivity to neutralization

Wed, 05/12/2021 - 21:41

Dear colleagues,

As you will see, all preliminary data in preprint, but there is a trend….

Ep 139-0: Journalists paper in Nature

Ep 139-1: Cherian in bioRxiv tracks the origin in Maharashtra and evidence of “convergent evolution”

Fig 3 shows how the key mutations accumulated over time: G142D; L452R; E484Q; P681R and Q1071H. Clearly, the 452 and 484 are common to other variants: Californian resp South-African + Brazilian and are located in RBD: may increase binding to ACE2 and be involved in immune escape. P681R is in common with the British variant and facilitates S1-S2 cleaving.

Ep 139-2: Yadav (India) in bioRxiv provides evidence of increased pathogenicity of this Indian variant as  compared to B1 D614G (the dominant strain in 2020) in Syrian hamsters.  Clearly more lung pathology and more weight loss.  Also higher viral load (VL) in nose and lung at day 3 and, remarkably (but possibly a consequence of higher VL) higher cross-neutralizing antibodies already at day 7.

Ep 139-3: Edara (US) in bioRxiv shows that sera from 24 convalescent patients, 15 Moderna and 10 Pfizer vaccinated subjects had on average 6 x lower neutralizing titers against a US B1.617.1 isolate than against a US wild type (WA1/2020), but most still were able to neutralize (except 2 convalescent sera).

Ep 139-4: Fereira in bioRxiv is a nice paper from UK and India that focuses on the role of the key mutations in the “Indian variant”, based on introduction of single and combined mutations in pseudoviruses (HIV particles with SARS-CoV-2 spike):

  • L452R, E484Q and P681R mediate entry into cells with slightly reduced efficiency compared to Wuhan-1. At first view counter-intuitive….
  • BUT: P681R mutation significantly augments syncytium formation upon the B.1.617.1 spike protein: contributing to increased pathogenesis in hamsters and infection growth rates observed in humans?
  • Tenfold reduced sensitivity to Pfizer vaccine-elicited antibodies (similar in magnitude to the loss of sensitivity conferred by L452R or E484Q alone)
  • Very interesting: March-April breakthrough infections in 33 HCW, vaccinated in January with Indian Astra-Zeneca (Covishield): majority were B.1.617.2, with a range of others (Fig 1E)

Ep 139-5: Hoffmann et al (Germany) in bioRxiv confirm that:

  • B.1.616 has only a limited advantage of cell entry in some cell lines,  (Fig 2 p.33)
  • Is less sensitive to neut by sera from convalescent patients or individuals vaccinated with Pfizer than WT virus, but the resistance of the South-African variant (B. 1.315) is clearly more pronounced (Fig 5 p. 36).

Ep 139-6: Yadav in a very preliminary bioRxiv preprint on sera from Covaxin recipients ( = Indian inactivated vaccine)

  • They neutralize the B.1.617 equally well as sera from convalescent patient (Fig 1 p. 10 E).  Most of these patients recovered from “wild type” (B1 11/17), but the 6 others had recovered from either the British (2), South-African (2) or Brazilian strain (2).  Not clear if there was any difference in neut between those different patients.
  •  The Covaxin recipients sera neutralized the wild-type and B.1.1.7 strains significantly, but just slightly (factor < 2) better than the “Indian” B.1.617. 

Ep 139.7: Unfortunately, I still do not find formal papers or preprints on the protection of vaccines towards  B.1.617.  There is this article in Business Today, with quotes from directors of famous Indian research institutes, claiming preliminary evidence that both Indian vaccines (the inactivated Covaxin and the Indian Astra-Zeneca, Covishield) protect against the Indian strain.  Without any concrete data…

Some preliminary conclusions:

  • There is some, but still limited experimental evidence that B.1.617 may be more infectious and more pathogenic than wild-type
  • This strain is less sensitive than WT or B.1.17 to sera from convalescent patients and mRNA vaccine recipients. In one study, ), B.1.617 is LESS resistant than B.1.315 (the South-African variant).
  • There are preliminary data that the Indian vaccines are protective against the Indian variant…

Best wishes,