Covid: Moderna/ J&J work ag delta virus and other variants; delta surging

 A recent preprint, pre-peer-reviewed article suggested that the Moderna mRNA vaccine should work against all four of the major SARS-CoV-2 variants, per measured neutralizing antibody titers (see covid moderna ag delta in dropbox, or https://www.biorxiv.org/content/10.1101/2021.06.28.449914v1.full.pdf ), based on company-sponsored study 

 

Details: 

-- sera from eight patient one week following dose 2 of the Moderna mRNA-1273 vaccine were evaluated for neutralizing antibody response to a variety of variants of concern: Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1) and Delta (B.1.617.2) 

    -- additionally, tests were done for the following variants of interest: B.1.1.526 (now called Iota, first identified in the US), A.23.1 (first identified in Uganda), B.1.525 (now called Eta, first identified in Nigeria), and A.VOI.V2  (first identified in Angola) 

-- see the above link to the text for more details about the specifics of the different variants of concern as well as variants of interest (see http://gmodestmedblogs.blogspot.com/2021/03/covid-variants-of-concern.html for definitions)

Results: 

-- as compared to the predominant variant in 2020 (D614G), neutralizing antibody titers were: 

    -- Alpha and A.23.1-v1, both comparable to D614G 

    -- variations of Beta: three were tested and were 6.9- to 8.4-fold reduced in neutralizing antibody response, with the Beta variant B.1.351-v3 having the lowest level, an 8.4-fold reduction 

    -- A.VOI.V2: 8-fold reduction 

    -- Gamma: 3.2-fold reduction 

    -- Delta: 2.1-fold reduction 

 

Here is their graph of variants and their reduction over D614G (VOC=variants of concern; VOI variants of interest)

 

 

 

 

 

Commentary: 

-- reductions found in this study were similar to a prior study for B.1.1.7, B.1.1.7+E484K, B.1.427/B.1.429, P.1, and B.1.351-v1 

-- the neutralizing antibody titers found are likely to translate to clinical protection from the variants, though we do not really know what titer of neutralizing antibody is truly protective

 

 

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also, just released is a small neutralizing antibody study finding that the J&J vaccine may well be effective against the Delta variant (see covid johnson vacc delta biorxiv2021 in dropbox, or https://www.biorxiv.org/content/10.1101/2021.07.01.450707v1.full.pdf  ). drug company study

 

Details:

-- 8 people were tested for neutralizing activity against several SARS-CoV-2 variants of concern 71 days after a single dose of the Johnson & Johnson vaccine 

    -- age range 47-91yo

-- lab tests: binding to B.1 spike and neutralization titers in a pseudovirus neutralization assay in variants of concern

 

Results:

-- Alpha variant: similar neutralization titers to initial SARS-CoV-2 strain

-- other strains: neutralization titers reduced 1.5-fold (for B.1.617) to 3.6 (for B.1.351, Beta)

    -- of these, the Beta and Gamma variants had the largest reductions (3.6- and 3.4-fold respectively)

    -- Delta variant had 1.6-fold reduction

-- computer analysis (referred to as in silico...) suggested the preservation of dominant T-cell epitopes in the Delta variant

 

--see their graph below. LOD=limit of detection

Commentary:

--A prior study found that this J&J vaccine was effective against the Beta and Gamma variants, with some depressed neutralizing activity. However, they did find levels comparable to the Wuhan initial virus for antibody-dependent cellular phagocytosis, complement deposition, and NK cell activation. also, CD4 and CD8 T-cell responses (including central memory and effector memory responses) [ie somewhat of a discordant but still a generalized immune response: a positive finding, since the Delta variant did relatively well in the above test, as compared to the Beta and Gamma variants]

    -- the original J&J study found a somewhat lower efficacy rate than the two mRNA vaccines in independent studies: moderate-to-severe illness was reduced 66%; severe-critical illness by 84% (though the latter included 96.9% in the confidence intervals).  see http://gmodestmedblogs.blogspot.com/2021/04/covid-j-vaccine-viral-load-after-vaccine.html . the vaccine efficacy rates were somewhat lower in South Africa, where 95% had the Beta variant, though there was complete clinical protections against Covid-19 hospitalizations and deaths

-- their finding of large decreases in the Beta and Gamma variants’ immune response is similar to what was found with mRNA vaccines.

-- As noted in prior blog (see http://gmodestmedblogs.blogspot.com/2021/06/covid-vaccine-effectiveness-for-b16172.html ), a real-world UK study did find that the Pfizer mRNA vaccine was clinically effective against the Delta virus, though the AstraZeneca one was less so (after 2 shots: Pfizer was 89% effective and AstraZeneca was 60% effective)

    -- this decrease with AstraZeneca raised concern about the J&J one, since it uses a similar adenovirus vector; but the J&J one was effective against severe cases in South Africa as noted above

    --but the finding of great clinical effectiveness of the Pfizer vaccine in the UK is really hopeful, given the similarity of the depressed lab-based immunologic responses with the J&J one (see http://gmodestmedblogs.blogspot.com/2021/06/covid-vaccine-effectiveness-for-b16172.html , which reviews the Pfizer vaccine’s neutralizing activity for several SARS-CoV-2 variants)

--other newer real-world studies (ie these studies are not controlled studies and have large inherent biases, such as who gets the vaccine, how much personal protection they use, how much exposure to the virus,...) have found somewhat less protection from the Pfizer vaccine, in areas where the Delta variant became the dominant one:

    --a Scottish study found 79% effectiveness against Delta variant: see covid scotland pfizer delta dec effectiveness lancet2021 in dropbox, or https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01358-1/fulltext : 2-doses of Pfizer led to 62% decrease in hospital admissions and 79% for Delta variant infection (75-82%)

    --a Canadian study found 87% effectiveness: see covid canada pfizer delta protection medrxiv2021 in dropbox, or https://www.medrxiv.org/content/10.1101/2021.06.28.21259420v1.full.pdf+html ): after full vaccination, protection was 87% (64-95%) against symptomatic infection

    --in Israel, concurrent with the spread of Delta variant, there was a "marked decline in the efficacy of the vaccine [pfizer] in preventing infection (64%) and symptomatic illness (64%), per the Ministry of Health there (see https://www.gov.il/en/departments/news/05072021-03 ), though i could not find a real study on this

Limitations: 

-- basic limitation here is that these are not clinical outcomes but neutralizing antibody outcomes. Other studies have suggested that neutralizing antibody titers are predictive of clinical responses (see http://gmodestmedblogs.blogspot.com/2021/06/covid-neutralizing-antibodies-predicts.html ), but we do not know for sure 

-- though we are accruing more information, we still do not know the relative individual or collective benefits of the different components of the broad immunologic response (ie: what is the protection from neutralizing antibodies vs cellular immunity vs innate immune system, both as individual components and in their web of interactions)

-- also these were extremely small studies, limiting the generalizability of the results. And we have no granular information about the eight subjects who were involved in each study. But, as noted above, the Pfizer vaccine did have decreased neutralizing antibodies against the Delta virus, and  the large real-world UK study with clinical outcomes did find it was effective against the Delta virus (see http://gmodestmedblogs.blogspot.com/2021/06/covid-vaccine-effectiveness-for-b16172.html  ). the other real-world studies still found significant protection, though some were a bit less than in the UK

 

So, the good news is that these vaccines seem to have adequate neutralizing antibody titers against all of the many SARS-CoV-2 variants so far. The potentially bad news is that the variants keep on coming, with variants of variants (making it really hard to keep track of all of these: ?need to expand nomenclature from the Greek to the Icelandic alphabet???) and that at some point in the future we are likely to have some non-vaccine susceptible ones.  

--which means we need to keep on identifying variants regularly and consistently, and as new genotypes emerge, assessing their susceptibility to vaccine.  (ie, lots of genetic testing)

--and we need to be especially aggressive to decrease the overall viral burden globally, leaving decreased ability for mutation development. Which really means vaccinate, vaccinate, vaccinate; and do so globally

    --the potential decreased effectiveness of the vaccines to the Delta variant in the "real-world" studies (as noted above, with pretty big differences between the studies) still suggest pretty impressive vaccine protection and only increase the imperative to vaccinate

--And, in our rapidly evolving situation, I personally think it is not a bad idea to continue wearing masks in enclosed settings even if vaccinated, and generally trying to remain somewhat distanced from others….  (just when we were feeling like life was returning to normal, perhaps really a “new normal”). 

and, per this morning, the Delta virus is now the dominant SARS-CoV-2 variant in the US, at 51.7%, with some areas having 80+% (eg Midwestern states of Missouri, Kansas and Iowa). for a chart of the growing percentages, see https://covid.cdc.gov/covid-data-tracker/#variant-proportions (which is a couple of weeks old). and the virus is really spreading in less-vaccinated areas!!!!

 

geoff

 

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Then go to "clinic", then to "clinical stuff" for articles, or go to https://www.dropbox.com/sh/nyle22q1fn6lkpk/AAB9B2hBj5Kw4gtrJAkI-UF8a?dl=0 for the powerpoint presentations

 

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or: go to https://www.bucommunitymedicine.org/ , a website from the Community Medicine section at Boston Medical Center.  This site does have a very searchable and accessible list of my blogs (though there have been a few that did not upload over the last year or two). but overall it is much easier to view blogs and displays more at a time.

 

 

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