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
5 Oct 2022 Episode 289: Omicron BA.2.75 revisited and the outlook for new variants, including BQ.1.1
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