25 March 2021 Variants and vaccines (3)

Thu, 03/25/2021 - 20:54

Dear colleagues,


The Astra-Zeneca saga and the threat by variants remain a focus of concern.  What have we learned over the last few days?


  1. Astra-Zeneca (AZ)


Ep 123-1: AZ proudly announced  the results of a large phase 3 (D8110C00001) with over 32,000 participants in the US, Peru and Chile. 

  • A 79% vaccine efficacy at preventing symptomatic COVID-19
  • 100% efficacy against severe or critical disease and hospitalisation
  • Comparable efficacy result across ethnicity and age, with 80% efficacy in participants aged 65 years and over

This was based on 2 doses (standard or low?) with 4 weeks in between, while in previous studies a longer interval was better


However, comments both Nature (Ep 123-2) and Science (Ep 123-3) call attention to the very unusual move of the Data Safety and Monitoring Board (DSMB), who published a letter in the Washington Post, saying that AZ press release was not based on the most recent data.  If those were taken into account, the efficacy was in the 69-74 % range.


As already mentioned in a previous Episode, the results in South-Africa, published last week in NEJM, suggest that AZ has very little if any protective effect against the SA variant (Ep 123-4).


Finally, a press release by Dr. Greinacher at the University of Greifswald (Ep 123-5) suggests that AZ could very rarely induce a syndrome referred to as  “vaccine-induced prothrombotic immune thrombocytopenia” (VIPIT).  The diagnosis can be made by finding anti-platelet factor 4  antibodies by immunoassay; and strong positivity in the newly developed functional test (platelet activation assay) in the presence of a newly identified cofactor (still under embargo).  Intravenous immunoglobulin (in addition to anti-coagulant) could be live-saving.


Clearly, while AZ offers a widely applicable (stored at 4)C),  rather cheap and reasonably efficacious vaccine, it has a lot of issues and many of those could have been avoided by a better (more correct, honest, modest, unpretending) scientific management ….. 


  1. Variants


British variant (B. 1.1.7)


Ep 123-6 by Volz in Nature confirms a 50 to 100 % higher transmissibility of the VOC.  Interesting Fig 3  p.7: both variants show similar distribution across ages: 19-49 around 60 %; 50-99 around 30 %  and children 10 %, but temporarily higher B1.1.7 in adolescents…



Ep 123-7 finds almost two-thirds higher case fatality of B1.1.7 than the previously circulating virus in this unvaccinated population




Ep 123-8 confirms earlier findings on the neutralization potential of convalescent sera or sera from Pfizer-vaccinated individuals against pseudoviruses displaying wild-type, B.1.1.7, or B.1.351 SARS-CoV-2 spike proteins. While vaccinee sera comparably neutralizes wild-type and B.1.1.7 pseudoviruses, the B.1.351 variant moderately resists vaccine-mediated neutralization, highlighting the importance of monitoring the emergence of variants. (see Fig 2 p. 29). 


Ep 123-9 Tada al perform a similar exercise, but they stress that the neutralization titers induced by Pfizer vaccination are only 3 times lower against the South-African variant BUT remain higher than the titers in convalescent serum against the  wild-type (with D614G).


Ep 123-10 Fauklner suggests that infection with the British variant B.1.1.7 induces antibodies with lower cross-neutralization against both Wuhan and South-African variant (B1.135).


Ep 123-11 Very interestingly, Moyo-Gwete shows that infection with the South-African variant (also called SARS-CoV-2 Y 505 V2) elicits strong cross-neutralizing antibodies.


Ep 123-12 Muecksch build further on the seminal paper of Gaebler (Ep 84-2).  They show that antibodies from memory B cells mature in vivo in convalescent individuals and acquire more mutations such that they become more potent and acquire a broader neutralizing activity, potentially even active against some variant SARS-CoV-2 viruses.  This is the consequence of persistence of SARS-CoV-2 in vivo  


Ep 123-13 Stamatatos shows that vaccination of previously wild type infected subjects induces very strong cross-neutralizing antibodies against for instance the South-African variant.


Notes: (1) Pseudoviruses are consistently more sensitive to neutralization than real viruses.

(2) Usually the pseudoviruses do not contain all the mutations of a variant.

(3) We do not know to what extent in vitro neutralization titers are predictive for protection.



  1. Other vaccine news


Ep 123-14: The Novavax S protein vaccine was also tested in South-Africa and shows an efficacy of 50 % against symptomatic B1.135 variant infections.  This protection was similar in SARS-COV-2 seropositive or seronegative participants.  HIV (+) subjects were also protected. Clearly, this result is better than the Astra-Zeneca (Ep 123-4).

Interestingly, in placebo participants, the attack rate of the new variant was similar in SARS-CoV-2 seronegative and seropositive subjects, suggesting that previous infection with the wild type virus did NOT protect against reinfection with B.1.135 .  (Table 2 p.24).


Ep 123-15 Very strong protection by 2 doses of Pfizer against SARS-CoV-2 infectionin highly exposed HCW in Jerusalem.


While Israel is the world champion in vaccinating Israeli citizens, including those who live in occupied Palestine, the Jewish State has not provided vaccines to the Palestinians living under Israeli occupation for > 50 years. According to MSF there is a surge of COVID disease, which cannot be handled by the fragile Palestinian infrastructure (Ep 123-16).  Meanwhile a first limited shipment of About 60,000 vaccines from WHO COVAX have arrived ( for a population of 5.2 million).    


Ep 123-18: A call in Nature to pool patents of SARS-CoV-2 vaccines to enable production on a larger scale and make sure that people in low income countries can also be vaccinated.


“Vaccine passports that enable citizens of some nations to travel internationally while millions of others wait for vaccinations will serve only to deepen global inequities.”


Best wishes,