25 Feb More on vaccines and variants

Thu, 02/25/2021 - 14:24

Episode 112 COVD-19 vaccines in the real world

Dear colleagues,

From several sides, I received and gatherd much wanted information on how well vaccination protects in real life, but I will also treat related, more general topics.  The vaccine results, I found are mostly from the Pfizer-BioNTech or the ChAdOx1 Astra-Zeneca, much less news from Moderna.

  1. Mixed news on Astra-Zeneca
  • Ep 112-1: in this Lancet paper of 19 Feb Voysey et al. try to clarify the persistent confusion on the real efficacy of AZ vaccine by analyzing data from 4 controlled trials together.  The main points:

Protection against symptomatic infection:

    • 66 % overall efficacy against symptomtic infection 14 days after 2 doses
    • Remarkably, “exploratory analysis” showed a 76 % efficacy between day 22 and 90 after a single dose.
    • Remarkably also, efficacy after 2 standard doses dependent on interval: from 55 % if < 6 weeks to 83 % if >  6 weeks.  

Protection against asymptomatic infection = puzzling:

  • Overall there is NO effect on asymptomatic infections by two standatrd doses and a 50 % reduction by the low dose-standard dose regimen (Table 1 upper panel)
  • However, when looking at the time interval between the two doses, there is an increase of asymptomatic infections if the time between the 2 doses is less than 8 weeks and a decrease if > 9 weeks!
  • Clearly, the number of observed asymptomatic cases is low.
  • Ep 112-2: the encouraging news comes from a preprint by Vasileiou on a 5 million cohort in Scotland: the first dose of either Pfizer or Astra-Zeneca provides a very good (80-90 %) protection against hospitalization from 1- 2 weeks after injection on. And this effect is similar in the 80 +   population.    Obviously, while these vaccines were rolled out, the “British” B117 variant was rapidly spreading.   

 

  • Ep 112-3: seemingly bad news from South-Africa (Madhi medRxiv 12 Feb 2021): A two-dose regimen of ChAdOx1-nCoV19 (high dose and short interval) did not show protection against mild-moderate Covid-19 due to (South-African) B.1.351 variant, however vaccine efficacy  against severe Covid-19 is undetermined .  For the latter reason, a trial with this AZ vaccine in 100,000 SA participats is awaited.   

 

  1. Good news on Pfizer with some warning
  • Ep 112-2: the encouraging result in Scotland; the following three are from Israel.
  • Ep 112-4: a retrospective sdtudy in over 9000 Israeli HCW shows a 30 % resp 75 % reduction of ALL SARS-CoV-2 infections 1-14 resp 15-28 days after the first Pfizer dose already ! As expected the reduction of SYMPTOMATIC infections is more impressive: 47% resp 85 %.  Testing was only done when symptomatic or afterv high risk contact, but those contacts occurred mostly OUTSIDE the workplace….
  • Ep 112-5: (Rossman medRxiv 9 Feb) the reduction in new COVID-19 cases and new hospitalizations is also clear in population-based studies: first seen in the older population who was also  first vaccinated. The interpretation of these data is complicated, because the vaccination campaign was performed during the “third wave” with also “third lockdown”….
  • Ep 112-6: Levine-Tiefenbrun (medRxiv 8 Feb) compared the viral load in over 2000 vaccinated and epidemiologically matched unvaccinated individuals: it was reduced 4 fold in the vaccinated individuals 12-28 days after 1st dose,  suggesting lower infectiosness and lower risk for disease.
  • Ep 112-7: A word of caution by Samanovic on vaccination of serpositive subjects (who have already antibodies by natural infection): these subjects show a strong Ab response to the first dose, but a blunted response to the second dose (see fig 1 p. 9).  The interpretation of these data is puzzling, as from Fig 1 C, it is clear that the neutralizing titers are similar in the end.  The real question therefore is about the duration of protection in both groups….

 

  1.   Some news on variants
  • Ep 112-8: Wibmer (medRxiv 19 Jan) shows that the South-African variant escapes or shows reduced susceptibility of neutralization towards some  monoclonal antibodies, but also towards SARS-CoV-2 convalescent serum (Fig 2 p. 7).
  • Ep 112-9: Stamatatos (medRxiV 6 Feb) investigated the susceptibility of the South-Afriucan variant (as compared to Wuhan SARS-CoV-2 Whuan and SARS-CoV-1) to neutralization by monoclonan Ab, but also by sera from COVID-19 recovered subjects, who received 1 dosis of Pfizer vaccine.  The result is shown in Fig 3 on p.28: neutralzing activity towards SA variant is very strongly boosted and almost similar to Wuhanb strain.  Also some neutralization towards SARS-CoV-1.  This “pseudovirus” assay is very sensitive and may overestimate the neut capacity in vivo.
  • Ep 112-11: New Californian variants (B.1.427 and B.1.429) with 5 mutations: (ORF1a: I4205V, ORF1b:D1183Y, S: S13I;W152C;L452R).  The latter L452R in spike may enhance the binding to the receptor.  It is also present in other states see https://outbreak.info/situation-reports?pango=B.1.429
  • Ep 112-12  according to a comment in Science, this variant behaves like the British or South-African: more contagious, more pathogenic and  less susceptible to neutralization: 4 X less for convalescent sera and 2 X less for Moderna or Pfizer vaccine recipients.  These data have not been published and it is not clear yet whether they really are “of concern”.

  

  1. Comparing different vaccines
  • Ep 112-13: A comment in Nature, reiterating the difficulty to compare the results from Pfizer-Moderna with Astra-Zeneca, because different populations, different time and place (with potential influence from variants).
  • Ep 112-14: Another comment in Nature about side effects confirms what we knew or suspected:
    • No deaths
    • Anaphylactic shock is rare: about 5 per million for mRNA vaccines, 10 per million for Astra-Zeneca. Poly-ethylene glycol is suspected. If so, Janssen Ad26 should be better…
    • Other local or systemic effects at a higher frequency than with Flu vaccine, but figures in COVID vaccine trials were much higher (50 + %) than recorded during roll-out !.   
  • Ep 112-15: Oguntunyo et al in mBio propose a pseudovirus neutralization assay, which could be used to standardize the results in various clinical studies.  At present, it is indeed impossible to compare those results, because of the wide variety of assays used.
  • Ep 112-16: The question whether the present COVD vaccines have transmission-blocking actrivity has not been answered in the trials. 
    • Moderna found two-thirds drop in the number of asymptomatic infections among people who received the first shot of the two-dose vaccine, but they tested people only twice, about a month apart, so might have missed infections.
    • AstraZeneca swabbed participants every week, and estimated a 49.3% reduction in asymptomatic infections among a subset of vaccinated participants compared with the unvaccinated group.
    • Ep 112-6 provides evidence of a lower viral load in “breakthrough” infection after first Pfizer dose in Israel.
    • More systematic cohort studies are underway in UK, Israel, Brazil, US….

  

  1. Miscelaneous
  • Ep 112-16: Vaccines are not the silver bullet. There are questions on accessibility, efficacy and vaccine hesitancy.  Hence good communication and preventive measures are much needed.
  • Ep 112-17: Nevertheless, CDC relaxes quarantine measures after full vaccination: https://www.yahoo.com/lifestyle/got-vaccine-still-quarantine-covid-185700997.html
  • Ep 112-18: Controversial trial in UK: deliberately infecting young people with COVID-19.
  • Ep 112-19: Importance of CD8 “killer” T cells in vaccine protection.  These cells target other epitopes than antibodies, therefore they could overcome the resistance from “antibody-escape variants.  However, killer T cells act only after infection, so rather prevent disease. In addition, to be fully active, other components than S should be included in the vaccines.  One could think that inactivated vaccines have advantage, but that is presumably not the case:
    • Inactivated vaccines with Alum do stimulate Ab , but not T cells so much
    • There are no data on T cell immunity with the “Chinese” vaccines (prepared with alum).

One could consider to include other proteins (e.g. Nucleocapsid or Membrane) in the RNA or vector vaccines and/or to improve the adjuvant (as is done in the Novavax S protein vaccine.  

 

That’s it for today.

 

Best wishes,

 

Guido

 

 

 

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