21 March 2021 Episode 122 Variants and vaccines update

Sun, 03/21/2021 - 20:12


Dear colleagues,

A new digest on recent literature, related to variants and vaccination.

But first: a very interesting reminder from Nat Reviews of what we all have learned on the immunology of COVID (Ep 122-1).  So many new findings in just one year ! 


  1. The News from Nature provides an overview of the main variants, circulating in the US (Ep 122-2):
    1. The New-Yorker B.1.526, combining the “Nelly” (N501Y) and EEK (E484K) mutation and clearly outcompeting others.  See Ep 122-3 Fig 1 and 2 p.11 and 12.
    2. Multiple variant Q677H/P mutation, arising in various part of US, but also in Egypt, Denmark and India. See Ep 122-4 fig 4 p. 22.
    3. The Californian B.1.427 and  B.1.429 with key mutation S13I and L452R See Ep 122-5 Fig 1 p.34


  1. A nice overview how the P.1 strain (with N501Y, K417N and E484K mutations amongst others) took over the epidemic in Manaus in less than 2 months between end of Nov and Jan, pushing aside previous strains such as B.1.128 and P.2, with a spectacular rise in hospitalizations (Ep 122-6).


  1. A deep sequencing exercise in over 1300 samples confirm that within host-diversity of SARS-CoV-2 is low, especially at high viral load (acute phase). Since diversity seems higher at lower viral load (i.e. late phase), one could suggest that escape mutations are generated and transmitted from those patients who do not eliminate the virus? (Ep 122-7)


  1. A very didactic paper on escape from neutralization after vaccination with mRNA vaccines (Ep 122-8).  A very nice overview of most important “variants of concern” on p.4 and of the relative neutralization resistance on p. 8.  So clearly, what we have to fear is the South-African variants, more so than the Brazilians….?


  1. The Madhi paper now in NEJM “nicely” shows that Astra-Zeneca vaccine was not effective against the South-African variant (Ep 122-9). 
  2. An optimistic view on the future in Nature Biotechnology (Ep 122-10) shows a list of novel concepts for the “next generation” COVID vaccines:
  • Virus-like particles e.g. Hep B-surface, combined with with the SpyCatcher/SpyTag),
  • Live-attenuated SARS-CoV-2 (based on codon-deoptimization);
  • CureVac and CEPI were co-developing portable mRNA printing technology, which could rapidly produce hundreds of thousands of vaccine doses in localized settings.
  • Subunit vaccines e.g. SARS-CoV-2 S conjugated ton tetanos toxoid or adjuvated with CpG1018
  • DNA vaccines:
  • Oral vaccines: Ad5 with S and N + TLR3 agonist
  • ….


  1. In this optimistic paper, also the inactivated Indian vaccine COVAXIN is mentioned: it is said to have an efficacy of 81 % in phase 3.  However, these data are unpublished.  A few days ago, the first publication on this vaccine appeared in iScience (Ep 122-11).  It is av  preclinical study, showing similar data as the Chinese inactivated vaccines.  The possible progress is that  the adjuvant IMGD is not just AlGel, but also contains a TLR7/8 agonist, which activates T cells as well.  


  1. A less optimistic view on the future in Nature on March 25: Herd Immunity for COVID-19 is probably impossible, even after vaccination (Ep 122-12). These are the reasons
  • Transmission blocking is probably not 100 %? Unclear at the moment
  • Large populations are un- or under-vaccinated
  • The new variants tend to escape
  • Immunity may wane
  • Human behavior: if transmission-blocking efficacy is 90 %, but after vaccination we see 10 people without protection instead of 1 now, we are back at square 1.

Obviously, those considerations are not a reason to give up on vaccination, since we do see the positive effects in terms of protection against hospitalization and death

  1.  The last paper is a letter in the Lancet, which clearly calls for international solidarity in vaccination efforts as the only way to get this pandemic under control (Ep 122-13).


Best wishes