After a short interruption, I found so much new interesting information that it is rather easy to pick the “low hanging fruits”. Here we go.
Evidence in favor of heterologous prime boost: Adeno + RNA
Ep 185-1: Callaway summarizes the evidence for Nature News. Most of it is “circumstantial”, but there are two really convincing papers:
Ep 185-2: Pozetto in Nature presents an observational study in over 13,000 HCW in the Lyon area, comparing Astra-Zeneca + Pfizer (heterologous) with twice Pfizer (homologous).
- Fig 1 shows that those who received Astra-Zeneca as prime and Pfizer as boost had an almost 50 % reduced chance on PCR + infection, as compared with Pfizer prime + boost.
- Fig 2 indicates that the neutralization of the heterologous regimen is more pronounced against Alpha, Beta, Gamma and Delta variants
- Fig 3 provides some explanation for the beneficial effects of heterologous regimen: more IgG class switched and activated memory B cells after the heterologous boost and more IFN-gamma producing CD4 T cells after the Astra-Zeneca prime.
Clearly, it looks as if the enhanced early CD4 T cell response after Astra-Zeneca sets the scene for better “maturation” and increased breath of the B cell responses.
Ep 185-3: Nordstrom in medRxiv presents a cohort study in the Swedish general population, comparing two heterologous regimens (Astra-Zeneca + either Pfizer or Moderna) with each of the homologous regimen: over 700,000 people in total. The outcome is symptomatic infection
- According to Pozetto Astra-Zeneca + Pfizer protects better against infection than homologous Pfizer.
- According to Nordsstrom the heterologous schemes are more protective against symptomatic infection than the Astra-Zeneca homologous scheme, but still inferior to both mRNA homologous schemes.
Efficacy of third dose:
- Healthy subjects (and general population)
Ep 185-4: A press release from Pfizer, announcing favorable results of a randomized phase 3 trial of a third dose in adults: “ A relative vaccine efficacy of 95.6% against disease during a period when Delta was the prevalent strain”
Ep 185-5: A “real world” observational study in Israel (Bar-On medRxiv) on third Pfizer dose: over 10 fold decrease in infection and disease as compared to two doses only.
Ep 185-6: Iketani meRxiv application of an heterologous third dose (Janssen Ad26COV-2 S) after two doses of Pfizer boosts Ab response and broadens it to variants of concern (alpha, beta, gamma, delta).
Ep 185-7: Maria Elena Romero (medRxiv): 3rd Pfizer dose 6 months after 2 doses in HCW: strong booster effect.
Ep 185-8: Wang medRiv A third booster dose of inactivated vaccine CoronaVac produces a high humoral immune
response via a sustained evolution of antibodies capable of effectively neutralizing SARS-CoV-2 variants of concern.
Ep 185-9: Lei Yue: similar message in Em Micr infect
- Immunosuppressed patients
Ep 185-10: Betrand in Kidney International on kidney transpla,nt patients under immune suppressive therapy:
- after a second dose of Pfizer 37 % seroconverted;
- after a third dose 61 % had Spike-specific antibodies.
Ep 185-11: Similar finding by Karaba (medRxiv), who used 70 % Pfizer and 30 % Jansssen vaccines report very similar findings on neutralizing antibodies. The third vaccine induced a very clear rise of neutralizing antibodies against all variants (see Fig2 p. 26) Neutralizing titres were, however, much lower than in healthy controls and 32 % of organ transplant patients remained negative.
Ep 185-12: Shroff (Nat Med) provided a third Pfizer dose to 20 patients with solid tumors on immune suppressive chemotherapy. Sixteen of those demonstrated a median three fold increase in neutralizing antibody titers.
There is a clear-cut immunological benefit of a third dose in terms of increased Spike antibody levels, neutralizing capacity and breath against variants in healthy persons, regardless whether mRNA, adenovirus or inactivated vaccines were used.
A similar, but less pronounced effect is seen in immune suppressed subjects (organ transplant and cancer), where increased seroconversion is observed.
The population study from Israel also suggests a clear-cut protective effect.
Ep 185-13: In round 14 of the UK REACT-1 study (REal-time Assessment of Community Transmission-1, two observations are striking for September:
- School children (5-17 yrs) are the most infected
- Vaccine efficacy against infection is waning: now at 45 % for Astra-Zeneca and 71 % for Pfizer.
Ep 185-14: FDA formally advises Pfizer vaccination for 5-12 years old children, after a careful weighing of risks and benefits in various scenarios of the epidemic. More information can also be found at the website of CDC
15 January 2022 Episode 223 Remarks on drugs and clinical aspects of omicron general and pediatrics
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10 Jan 2022 Episode 220 Why we should have vaccinated our (grand)children the day before yesterday
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9 Jan 2022 Episode 219 Protection against MISC and more on therapeutic antibodies or soluble ACE-2 against omicron
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8 Jan 2022 Episode 218 Children and omicron. COVID and diabetes. VE of booster in elderly
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6 Jan 2022 Episode 217 Pre-omicron children and BTI; Omicron: rapid tests, T and B responses, therapeutic antibodies
> More info