COVID: the new vaccine trial

as has hit the press recently and forcefully, Moderna has a new vaccine that shows some preliminary positive results, leading among other things to big increases in the Dow Jones average. And the company’s stock valuation surged to $22 billion (it is more than tripled in this year), which, as noted in STAT news, is “an astonishing feat for a company that currently sells zero products”, and has propelled its CEO into the billionaire class

 

Unfortunately, it is hard to fully assess the content of the study, since only the Moderna press release has been published

 

the National Institute for Allergy and Infectious Diseases (NIAID) partnered with Moderna, developed the vaccine along with some Moderna scientists (see https://www.niaid.nih.gov/news-events/nih-clinical-trial-investigational-vaccine-covid-19-begins), and is running the phase 1 trial, yet (perhaps significantly) NIAID has not provided any comment on the Moderna announcement (see https://www.statnews.com/2020/05/19/vaccine-experts-say-moderna-didnt-produce-data-critical-to-assessing-covid-19-vaccine/)

 

Per the Moderna press release (see https://investors.modernatx.com/news-releases/news-release-details/moderna-announces-positive-interim-phase-1-data-its-mrna-vaccine?mod=article_inline ):

-- the vaccine is an mRNA vaccine against SARS-CoV-2 encoding for a pre-fusion stabilized form of the Spike protein (again, largely developed by NIAID)

-- in 45 patients aged 18 to 55, after 2 doses of the 25 µg and 100 µg vaccine, or one dose of the 250 µg dose, the “levels of binding antibodies” were at least “the levels seen in convalescent sera from people have recovered from Covid-19”

-- in the 8 patients for whom neutralizing antibody data are available: at day 43 there were neutralizing antibodies in all 8 “and these levels were at or above the levels generally seen in convalescent sera”

-- the vaccine was generally safe and well-tolerated with a single person developing grade 3 erythema at the injection site

-- mice do well: viral replication in the lungs was prevented by the vaccine, and neutralizing antibodies were at a level found to be protective in the mouse challenge model

-- they conclude that in this interim phase 1 trial, vaccination elicited an immune response of the magnitude caused by natural infection

 

Commentary:

--there was a really good article on this vaccine in STAT news: see https://www.statnews.com/2020/05/19/vaccine-experts-say-moderna-didnt-produce-data-critical-to-assessing-covid-19-vaccine// , making some of the points i made above and below

-- it cannot be too strongly stated that the above findings are largely uninterpretable, despite the huge infusion of money from the US government to Moderna (a mere $483 million), massive assistance from the federal NIAID (ie, us taxpayers), and the attendant huge financial benefits for the drug company and its CEO:

    -- we have no data on who these 45 patients were: their age, comorbidities, etc (might be a pretty different vaccine response in healthy 19-year-olds than in very sick 45-year-olds)

    -- this is a very small trial: we have a lot of studies from prior trials with other vaccines, that preliminary data does not predict future success (e.g. with the early dengue vaccine that led to much more dangerous subsequent dengue infections in kids; or the Lyme vaccine that ultimately proved to cause lots of arthritis; or the rotavirus vaccine leading to intussusception in kids)

        -- and, though a very large number of the global population is likely to get infected with SARS-CoV2, that number is likely to pale as compared to the very very large number of people who might get the vaccine: a small percent of really bad vaccine outcomes, not likely to be seen in these small studies, might translate into a very large number of people who sustain them, potentially being much more dangerous than getting the actual virus (which is still pretty benign in about 80% of people). The problems with the dengue, Lyme, and rotavirus vaccines only became apparent after they were approved and given to lots of people

-- we also don’t really know what they mean by several of their comments:

    -- what are the levels of binding antibodies that they consider significant? We do know that many people seem to have antibodies that are not protective. So what are these binding antibodies and do they really matter? see http://gmodestmedblogs.blogspot.com/2020/05/covid-reinfection-cases-and-risk.html

    -- they comment on 8 patients (not a lot) all having levels of neutralizing antibodies (these antibodies are likely to be the effective ones) “at or above the levels generally seen in convalescent sera”. Well, these levels vary from person to person after Covid-19, and some never develop neutralizing antibodies, or at only a very low level. And the best guess is that these levels should be on the order of a 1:1024 dilution level (see http://gmodestmedblogs.blogspot.com/2020/03/covid-using-convalescent-serum-to-treat.html). We have no idea what they are using as their cutpoints for calling them “effective” levels. and what do they really mean by levels as seen in natural infections when these can be zero??

    -- and how durable are these antibody responses? We don’t even know how durable they are with real infection, so these both need to be understood and compared

    -- as pointed out in the STAT article: Moderna had been more forthcoming with data about a phase I trial for CMV vaccine. So, what does it mean that they are providing such limited data on this SARS-CoV-2 one??

 

So, these are really big issues.

-- these are very preliminary findings, and should not be generalized beyond their very limited scope. on a scientific level, it is absurd to broadly release results without the ability to really interpret them...

-- many vaccines initially seem great, but many of them ultimately end up in the trashbin of vaccine history, some causing more problems than they might have prevented

-- and, though we are all hungry for positive results to in this current scourge (and realize that the only real solution is to get an effective vaccine), it is very premature to assume that this is the one. Fortunately, there are over 100 vaccines being tested, and hopefully one or more will be useful either singly or in combination

-- but, in some ways my real concern is a political one: that the Trump administration will use these very preliminary results to undercut their disastrous denial of the dangers of this virus early on, by on the one hand continuing to blame others for their failures (e.g. China, WHO, etc ) while promoting themselves (and their political prospects) over this "great" new vaccine

geoff

 

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