Pfizer and BioNTech on Monday announced that the most advanced of four COVID-19 vaccine candidates from their BNT162 mRNA-based vaccine programme demonstrated the ability to elicit high SARS-CoV-2 neutralising titers after the second dose in an ongoing Phase I/II study in Germany. The results, which were published on the MedRxiv preprint manuscript server, also showed that the BNT162b1 candidate vaccine induced strong CD4+ and CD8+ T-cell responses.
"It is encouraging that the data on BNT162b1 from the German study cohort are very much in line with what we have seen in the US study cohort," remarked Özlem Türeci, chief medical officer of BioNTech. Türeci added "the preliminary data indicate that our mRNA-based vaccine was able to stimulate antibody as well as T-cell responses at remarkably low dose levels."
Earlier this month, the companies reported positive early results from the trial's US cohort, showing that BNT162b1 led to higher levels of antibodies than convalescing COVID-19 patients at day 28, seven days after study participants had received a second dose (for related analysis, see ViewPoints: BioNTech and Pfizer boost COVID-19 vaccine hopes).
Preliminary data for BNT162b1 in the German cohort evaluated the vaccine in 60 healthy adults 18 to 55 years of age. Of these, a total of 48 subjects were vaccinated with the 1 mcg, 10 mcg, 30 mcg or 50 mcg does on days 1 and 22, while another 12 received a single injection of 60 mcg.
'Broad neutralising activity'
Pfizer and BioNTech reported that SARS-CoV-2 neutralising geometric mean titers on day 43 were dose level-dependent, ranging from 0.7-fold for the 1-mcg dose, to 3.2-fold for the 50-mcg dose, compared to that of a panel of convalescent human sera. Further, they noted that sera of vaccinated subjects displayed "broadly neutralising activity" in pseudovirus neutralisation assays across a panel of 16 SARS-CoV-2 receptor binding domain (RBD) variants.
Meanwhile, T-cell responses varied between subjects, with no clear dose-level dependency of the response between the 1- to 50-mcg groups, "indicating that stimulation and robust expansion of T cells might be accomplished at low mRNA dose levels," the companies said. They reported that 29 of 36 subjects also mounted an RBD-specific functional, CD8+ T-cell response that was comparable to memory responses observed against cytomegalovirus, Epstein Barr virus and influenza.
In terms of safety, the companies said local reactions and systemic events after injection with BNT162b1 at all dose levels were "transient, generally mild-to-moderate, with occasional severe events of influenza-like symptoms and injection-site reactions." They noted that all adverse events resolved spontaneously and were managed with simple measures.
Late-stage testing may start later in July
Data from the US and German cohorts of the study will be used to help determine a dose level and select among multiple vaccine candidates to advance to later-stage testing. A Phase II/III trial with 30,000 participants is expected to start this month if the companies receive regulatory approval. Pfizer and BioNTech recently said they want to file their coronavirus vaccine by December, and if all goes well, they expect to manufacture up to 100 million doses by the end of 2020, and potentially more than 1.3 billion doses by the end of 2021.
Separately, AstraZeneca reported that its Oxford University-partnered vaccine AZD1222 against COVID-19 increased levels of both neutralising antibodies and T-cells that target the SARS-CoV-2 virus in a Phase I/II study. The findings were published Monday in The Lancet. Also on Monday, the UK government announced that it secured early access to 30 million doses of the BNT162 mRNA-based vaccine candidate.
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