4 February 2022 Episode 235 Vaccines and antigen tests human challenges

Episode 235

Dear colleagues,

In this « light » episode, I will discuss some recent papers (mostly preprints) on vaccine immune responses and efficacy-effectiveness as well as antigen detection.  

With regard to the latter, it is again evident that the brand and the conditions of use do matter a lot  (see Ep 235 6-9) !! This is an important tool to mitigate outbreaks, but it is really urgent that national and European authorities organize quality control and only allow selling tests with a sensitivity of at least 80 % for the circulating variant.    That is absolutely NOT the case today. See for instance Ep 235-9  

1. More on vaccine-induced immune responses and  efficacvy/effectiveness

Ep 235-1 A:  Results of ENSEMBLE 2 (finally). It is a phase 3 trial with 2 doses of the Janssen (J&J) Ad26.COV2.S.  This trial was already finished in June 2021 and included over 14,000 participants  

Findings:  

• Efficacy of 75.2% against moderate to severe–critical Covid-19 and 100% against severe–critical Covid-19 by ≥14 days after boosting.
• No cases requiring medical intervention and no Covid-19-related deaths were observed in the active arm of the study.
• Additionally, vaccination reduced the duration, number, and severity of symptoms in breakthrough cases, suggesting a shift from more severe to milder Covid-19 infection.

Ep 235-1 B:  Sisonké trial in over 200,000 South-African HCW 6-9 months after first dose during emergence of Omicron: booster , vaccine effectiveness of J&J against hospitalization was 63% (0-13 days after booster) to 84-85 % 14-27 days, and 1-2 months post-boost.

Clearly, in (part of) a world where mRNA vaccines are not available, J&J remains a  good vaccine

Ep 235-2: Vanshylla medRxiv 2 Feb  Durability of Omicron-neutralizing serum activity following mRNA booster immunization in elderly individuals

Elderly (76-96 yrs) 2 doses of Pfizer, followed wit booster after 7 months

V1 = 4 wks after 2nd dose; V2 = 5 months after 2nd dose; V3 = 1 mo after 3rd dose; V4 = 4.5 mo after 3rd

Very low titers to omicron are strongly boosted and remain elevated (lower than delta or Wuhan)

Ep 235-3: Naranbai medRxiv 5 Jan 2022 T cell reactivity to the SARS-CoV-2 Omicron variant is preserved in most but not all prior infected and vaccinated individuals

Adult volunteers 37-60 yrs old

Most vaccinated subjects have good T cell responses (interferon-gamma ELISPOT) against both WT, Delta and Omicron Spike peptides, but lower levels than in infected (+/- vaccinated) subjects

Interferon-gamma ELISPOT to Omicron is strongly enhanced by boost

Some vaccinated individuals, even after infection and boosting, fail to generate Spike-specific proliferating CD4 and CD8 T cell responses: are they more vulnerable to disease?? 

Ep 235-4 : Kislaya 2 Feb medRxiv:  Comparing delta and omicron breakthrough in Portugal

Not surprisingly: Omicron much more than Delta breakthrough infections

• After full vaccination: OR Omicron/delta = 2.1 (1.8- 2.4)
• After full vacc + booster: OR Om/delta = 5.2 (3.1 to 8.8) !!

Interestingly: no difference in viral load between omicron and delta

Lower efficacy of Astra-Zeneca vs Pfizer after full vaccination is wiped out by Pfizer booster

Ep 235-5:  Bar-On medRxiv   Protection by 4th dose of BNT162b2 against Omicron in Israel

People aged 60+ could receive a fourth dose of Pfizer at least 4 months after 3rd dose

Comparison of rate of confirmed Covid-19 and severe illness between those who had received a fourth dose at least 12 days earlier, those who had received only three doses, and those 3 to 7 days after receiving the fourth dose.

Clearly, from 12 days after 4th dose, the rate of infection is 2 X lower and the rate of severe illnerss is 4.3 X lower as compared to those who received only 3 doses.

(Between 3-7 days after 4th dose, there is no effect yet).  

CONCLUSIONS:

• J&J is a good vaccine to prevent severe disease, including omicron.  
• Even in elderly, a booster with Pfizer induces good levels of anti-omicron Ab that persist for several months
• In middle aged subjects interferon-gamma producing T cells against omicron Spike are induced by 2 dose vaccination and strongly boosted with a third dose, although infection induces higher (and broader) T cell responses.  Some individuals in all groups have proliferating CD4 and CD8 T cells.
• Pfizer booster after Pfizer or Astra-Zeneca induces similar protection against delta and lower against omicron in Portugal
• In 60 + Israeli, the fourth dose of Pfizer prevented infection by 50 % and severe illnnes by 75 % as compared to 3 doses.

2. Rapid testing on Omicron

Ep 235-6: Paula de Michelena medRxiv  2 Feb ’22 Real-life performance of Panbio rapid antigen test

Convenience sample of 244 consecutive subjects (age 2-96 yrs): naso-pharyngal swabs

Ep 235-7: Landaverde medRxiv 1 Feb 2022 Comparison of BINAX now and PCR on anterior nares swabs; calculated sensitivity of only 52.1%, specificity of 100%: clearly only samples with low Ct < 26 (high viral load) detected!

Ep 235-8: Landon medRxiv 2 Feb 2022: High Rates of Rapid Antigen Test Positivity After 5 days of Isolation for COVID-19 in HCM, regardless of symptoms

Very remarkable that boosted individuals tended higher positivity on day 5-6!

Tentative explanation: they become symptomatic earlier (because of boosted immune response), hence the diagnosis is made earlier?

Implication: Inclusion of individuals on day 6-10 of illness in community or work settings may increase the risk of COVID-19 spread to others which, in turn, may undermine the intended benefits to staffing by resulting in more sick workers.

Ep 235-8:  A long lit of evaluations by the Paul Ehrlich Institute dated 12 Jan, so presumable most tests done before Omicron shows the enormous differences in sensitivities of various brands of antigen tests. As far as I understand, all these tests have a CE label and can be freely sold in the EU. We need order in this chaos

3. Human challenge Ep 235-9 A and B Wuhan strain in healthy young volunteers (M/F)

Some important findings:

• First sign of PCR already 2 days after infection; by lateral flow (LFA or antigen detection; but brand not clear) 1-2 days later than PCR but LFA faithfully predicts cultivable virus by Focus Forming Assay (FFA);  high viral loads persisted for up to 12 days.

• Symptoms: A minority of participants showed symptoms (see below).  Remarkably, however, 70 % had loss of taste and smell, which persisted for 6 months in 5 people. No quantifiable relation between viral load and symptoms  

• Interestingly, since lateral flow test was strongly associated with viable virus, modeling showed that twice weekly testing could diagnose infection before 70-80 % of viable virus had been generated.

Ep 235-10:  Summary of COVD immunology for non-immunologists in Nature Briefing.   Reiteration of many concepts that I introduced in previous episodes.  Please, non-immunologists, take the time to read and ask me for clarification if needed !!