8 May 2021 Episode 138 Vaccine efficacy against SA variant and controversy over SARS-CoV-2 integration

Sat, 05/08/2021 - 17:08

Episode 138 : Efficacy of various vaccines against variants and integration of SARS-CoV-2 RNA

Vaccines against South African variant B.1.315

Ep 138-1: Good news in Nature that Pfizer vaccine is 75 % effective against the South-African variant and that also Novavax S protein is about 50 % effective. As always, I’ll trey to put this “breaking news” into perspective.

Ep 138-2: The Pfizer data are actually from Qatar. It is not entirely clear whether it is protection against infection or symptomatic disease. Interestingly,

  • Overall protection against British B.1.1.7 was 29.5 % after one dose and 89.5 % > 14 d after 2 doses, while for South-African (B1.315) the figures were 16.9 and 75 %.
  • Protection against severe disease was  against B.1.1.7 was 50 and 100, for B.1.315 0 and 100 % after first and 14 days after 2nd dose respectively.

Ep 138-3: The Novavax S protein (with Th1 skewing adjuvant) after 2 doses had an overall efficacy of about 50 % against mild-to-moderate COVID in South-Africa at the time of B.1.315 became dominant.  There is no mention of effects after one dose, nor about severe cases. Remarkably,  the protection was NOT clear in the HIV(+) subset (but numbers were low) and there was NO additional beneficial effect of being seropositive for COVID (past infection with wild-type).

Ep 138-4: Reminder that 2 doses of Astra-Zeneca really seems to have no appreciable efficacy (about 10 %) against B.1.315 (Fig 3 p.11).  Fig 2 p. 8 also shows that induction of neutralizing Ab against this variant was equally very weak, both after natural infection with the original virus or after Astra-Zeneca vaccination.   

In all fairness, we have to add that they used the “suboptimal” (standard) dosing scheme with only about 1 month interval.  As you might remember, this regimen was only 60 % effective in UK (before the arrival of B.1.1.7), while the now standard regimen with a low dose prime and a boost with standard dose after 12 weeks was 90 % effective in the very complicated Lancer paper of 8 Dec (Voysey https://doi.org/10.1016/S0140-6736(20)32661-1).

Ep 138-5: Result of ongoing “Ensemble single dose trial” of J&J, which shows an “overall” efficacy of 66 % against mild-to-moderate COVID and 74 resp 85 % protection against severe COVID 14 resp 28 days after vaccination.  (Table 2)

The substudy in South-Africa vaccine efficacy was maintained: 52.0% against moderate to severe–critical disease and 73.1% against severe–critical disease with onset ≥14 days after administration; 64.0% against moderate to severe–critical disease and 81.7% against severe–critical disease with onset at ≥28 days after administration.

Remember also the results of the NHP trial (Ep 137-4), where it was clearly shown that a second dose could lift the neutralizing antibody titers against B.1.315 significantly to a level that approached the titers of a single dose vaccine against wild-type (Fig 6 p. 9 of EP 137-4)

Ep 138-6: a recent Science paper showing that a single dose of the Pfizer vaccine, applied in people previously infected with wild type, enhanced both B and T cell responses, including  very high titers of Neut Ab against B.1.315.  This favorable result seems in clear contrast with Astra-Zeneca (see Ep 138-4 above).

 

Conclusion:    

  • It seems clear now that Pfizer (and presumable also Moderna) are the best available vaccines against B.1.315.  
  • J&J performs well and might be further improved by just adding a second dose (2-3 months after the 1st?), but then it loses its logistic advantage of being the only “ single dose vaccine” of course.
  • Novavax just reaches the 50 % efficacy threshold.     
  • I would be surprised that Astra-Zeneca could still be “rescued” for this indication.  

Critical note: despite the successful “vaccine diplomacy” by China and (to a lesser extent) by Russia, which has convinced WHO apparently, there are, to my knowledge, no publicly available data about the activity of those vaccines against the South-African variant.  (See Ep 137-7 and -8)

 

Controversy over integration of SARS-CoV-2

Ep 138-9/10: Jon Cohen discusses the controversial paper by Zhang et al, that provides evidence on integration of some parts of the SARS-CoV-2 RNA genome into the human DNA. It is at the 3’ end- hence the structural proteins mainly N and not the polymerase.  This could be done by LINE-1 (long interspersed nuclear element-1), which is a retrotransposon remnant of retroviruses in human cells ( see: https://en.wikipedia.org/wiki/Long_interspersed_nuclear_element).

The reverse-transcribed elements in DNA will remain the cell, even after active infection is over.  They could be transcribed again in RNA and give rise to positive PCR after “clinical cure”, potentially explaining persistently positive PCR that is not cultivable and not transmissible.  See Ep 138-11 Table 2 p. 6.

This paper (in preprint as of Dec) has raised a lot of scientific, but also public controversy.  It was wrongly interpreted as if the mRNA vaccines could also potentially cause genetic modifications and even fertility problems.

Best wishes,

Guido  

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