- The experimental coronavirus vaccine Pfizer and BioNTech selected for late-stage testing in tens of thousands of people caused fewer side effects than an earlier version, new study results made available online Thursday showed.
- Pfizer and BioNTech, partners in vaccine development, had cited the shot's better safety profile in choosing to advance it into late-stage trials last month. The data disclosed Thursday support their decision, showing the selected vaccine, dubbed BNT162b2, in particular led to fewer cases of fever than the first version.
- The two versions, which target slightly different segments of SARS-CoV-2, both spurred similar immune response in the companies' study, according to the data. But regulators will be focusing on vaccine safety just as much as effectiveness when they consider whether a coronavirus vaccine merits approval. A shot with higher incidence of side effects, even if effective, wouldn't be as good a candidate for a mass vaccination campaign.
When Pfizer and BioNTech decided they were going to advance BNT162b2, they had only released data from early stage trials of a slightly different candidate, called BNT162b1. Both use messenger RNA to instruct cells to make viral proteins in an attempt to stimulate an immune response; the difference is that cells receiving b1 make part of the SARS-CoV-2 virus' "spike" protein, while b2 stimulates production of the entire protein.
While the data — published on the medical pre-print server medRxiv — don't show b2 results in a more robust immune response, they do suggest a safer shot.
In the case of b1, three-quarters of patients aged 18 to 55 and one-third of patients aged 65 to 85 experienced fever after the second of two shots of either 10 or 30 micrograms. For b2 at 30 micrograms, 17% of patients 18 to 55 and 8% of those 65 to 85 reported fever after the second dose.
By comparison, Phase 1 results showed Moderna's vaccine mRNA-1273, which also uses mRNA, led to fever in 40% of patients injected with the 100-microgram dose selected for Phase 3 trials.
As the Phase 1 trial was aimed at safety, the Pfizer and BioNTech researchers couldn't make conclusions about b2's ability to prevent disease. Proving that it can is the main goal of an ongoing Phase 3 trial, which Pfizer said on Thursday has enrolled 11,000 of an expected 30,000 subjects in the three weeks since starting.
However, immune responses as measured by so-called "neutralizing antibodies" to the spike protein were equal to or greater than levels seen in the blood of patients who have recovered from COVID-19. In patients aged 65 to 85, the antibody levels ranged from one to nearly two times that of recovered patients depending on dose or specific vaccine, and in patients 18 to 55 the levels were nearly three to four times recovered patients.
The researchers cautioned their data is very preliminary, as the 156 patients had only been assessed through seven days following the second of two doses. Moreover, the significance of the immune response can't be fully evaluated because it is unknown what level of antibody or immune-cell response is sufficient to protect against disease, they wrote.
Lasting immunity to SARS-CoV-2 could require involvement from other parts of the immune system, too. A small German trial of b1 showed the vaccine stimulated a response from immune cells which both fight the virus but also provide an "immune memory" for later defense against infection.
That might be an important part of Pfizer and BioNTech's vaccine's ability to address COVID-19, Evercore ISI analyst Umer Raffat wrote in a note to clients. The weaker antibody response in older patients and the likelihood that their levels will fade means those immune cells could be critical, he wrote.
Pfizer launched its Phase 3 trial in late July, shortly after Moderna. Both companies plan to enroll tens of thousands of participants in their respective studies, and could potentially have initial data to take to regulators by the fall.