Today saw publications from three groups developing Covid-19 vaccines (as per the title). Short form: all raise an apparently appropriate immune response, and none causes dangerous side effects. Pfizer’s preprint outlines T-cell response, missing from their initial paper.
First let’s get all of the links on the record: the papers themselves, and Derek Lowe’s writeup on each paper at ScienceMag.org. As faithful followers of this blog will be aware, I depend on Lowe for close readings of such papers and for explanations thereof that are (semi-) comprehensible to a technically literate but biologically lightweight audience (such as I). For completeness, links for Moderna’s candidate are also included; its initial Phase I results came out last week.
- Oxford / AstraZeneca: paper, Lowe
- Pfizer / BioNTech: preprint, Lowe
- CanSino: paper, Lowe
- Moderna: paper, Lowe
First, side effects: all candidate vaccines described so far engendered some mild flu-vaccine-like reactions: soreness at the point of injection, tiredness, sometimes muscle or joint pain, headache, or slight fever. Those reported for Moderna’s vaccine seemed to be the strongest, but no serious adverse effects occurred from any of the candidates.
The Oxford / AstraZeneca results for candidate ChAdOx1: This effort has been getting quite a lot of exposure in recent days, including this admiring portrait of its leader, Sarah Gilbert. The Oxford candidate is built on a viral vector: an adenovirus that causes a cold in chimpanzees, but has not infected humans (so we don’t raise an immune response to the viral vector before the vaccine has a chance to do its work). The results: the vaccine raised antibodies to SARS-CoV-2, which peaked around day 28 and persisted to day 56 with some decline. Subjects who received a booster shot (most did not) showed significantly higher antibody titers. This was especially true for the neutralizing antibodies capable of disabling SARS-CoV-2. There was a T-cell response, which peaked at day 14 and persisted out to day 56; the booster did not affect the levels of T-cells for those who received it.
The Pfizer / BioNTech results for candidate BNT162b1: As noted, the group has produced a second paper outlining further results from their Phase I studies; this one is a preprint, not yet peer-reviewed. With this mRNA vaccine antibody production began somewhere between day 8 and day 22 — when most subjects got a booster, which raised antibody levels 10-fold. As for neutralizing antibodies, at higher dosages subjects showed levels comparable to the upper ranges of what is seen in patients who clear the virus. T-cells: Pfizer’s candidate showed robust production of both CD4+ and CD8+ T-cells, whereas the Moderna vaccine was considerably weaker in CD8+. Follow the Lowe link for much more on this. Another interesting aspect of Pfizer’s new paper: they reported their candidate’s effectiveness against 17 different mutations of SARS-CoV-2, and it seems to be about equally effective against all of them.
The CanSino results for their Ad5-vectored candidate: This vaccine rides upon another adenovirus, called Ad5. Unlike Oxford’s, CanSino’s viral vector is present in humans — according to Lowe, 50% of people in China carry antibodies to Ad5, 30% in the US, 80% in India. This means that significant fractions of a population will probably fight the vaccine itself with an initial immune response. This conclusion seems borne out in the results. The vaccine caused the body to produce antibodies, but at levels 2x-3x lower for those subjects who had already been exposed to Ad5. At each of the two dosing levels trialled, the vaccine caused T-cell production, and previous exposure to Ad5 did not affect this. The group did not report data on CD4+ versus CD8+ production.
CanSino is a Chinese company, and some observers have wondered whether, should their candidate vaccine win the race, its production would be reserved initially for Chinese citizens. (To be fair, some wonder the same about vaccines invented in America, and elsewhere.)