Oxford vaccine activates immune response against COVID-19
The chimpanzee adenovirus-vectored vaccine (ChAdOx1 nCoV-19) expressing the SARS-CoV-2 spike protein exhibits an acceptable safety profile and induces both humoral and cellular immune responses against the novel coronarvirus disease (COVID-19), results of a phase I/II trial by the University of Oxford in UK have shown.
“ChAdOx1 nCoV-19 was safe, tolerated, and immunogenic, while reactogenicity was reduced with paracetamol,” the researchers said. “A single dose elicited both humoral and cellular responses against SARS-CoV-2, with a booster immunization augmenting neutralizing antibody titres.”
Between 23 April and 21 May 2020, 1,077 healthy adults aged 18–55 years with no history of laboratory-confirmed SARS-CoV-2 infection or of COVID-19-like symptoms were enrolled in five trial sites in the UK and randomized to receive either ChAdOx1 nCoV-19 (n=543) at a dose of 5 x 1010 viral particles or a meningococcal conjugate vaccine (MenACWY; n=534).
In addition, 10 participants assigned to a nonrandomized, unblinded ChAdOx1 nCoV-19 prime-boost group received a two-dose schedule, with the booster vaccine administered 28 days after the first dose.
The researchers assessed humoral responses at baseline and following vaccination using a standardized total IgG ELISA against trimeric SARS-CoV-2 spike protein, a multiplexed immunoassay, three live SARS-CoV-2 neutralization assays, and a pseudovirus neutralization assay, as well as cellular responses using an ex-vivo interferon-γ enzyme-linked immunospot assay.
More individuals in the ChAdOx1 nCoV-19 group had local and systemic reactions, many of which were reduced by use of prophylactic paracetamol, including pain, chills, headache, feeling feverish, muscle ache, and malaise (p<0.05 for all). No serious adverse events were related to ChAdOx1 nCoV-19. [Lancet 2020;doi:10.1016/S0140-6736(20)31604-4]
Spike-specific T-cell responses in the ChAdOx1 nCoV-19 group peaked on day 14 (median, 856 spot-forming cells per million peripheral blood mononuclear cells, interquartile range [IQR], 493–1802; n=43), while anti-spike IgG responses rose by day 28 (median, 157 ELISA units [EU], IQR, 96–317; n=127) and further increased following a second dose (median, 639 EU, IQR, 360–792; n=10).
Thirty-two (91 percent) of 35 participants demonstrated neutralizing antibody responses against SARS-CoV-2 after a single dose when measured in MNA80, while all 35 participants (100 percent) showed such responses when measured in PRNT50. Following a booster dose, all participants had neutralizing activity: nine of nine in MNA80 at day 42 and 10 of 10 in Marburg VN on day 56.
Of note, neutralizing antibody responses was strongly associated with antibody levels measured by ELISA (R2, 0.67 by Marburg VN; p<0.001).
“Neutralizing antibodies targeting different epitopes of the spike glycoprotein have been associated with protection from COVID-19 in early preclinical rhesus macaque studies,” the researchers said. “Although a correlate of protection has not been defined for COVID-19, high levels of neutralizing antibodies have been shown in convalescent individuals, with a wide range, as confirmed in our study.” [Science 2020;doi:10.1126/science.abc6284; Nature 2020;doi:10.1038/s41586-020-2456-9; Clin Infect Dis 2020;doi:10.1093/cid/ciaa721ciaa721]
Furthermore, mounting evidence suggests that T-cell responses could mitigate COVID-19. A robust memory T-cell response without symptomatic disease in the absence of a measurable humoral response was detected in individuals who were exposed but asymptomatic. [Cell 2020;181(501.e15):1489; bioRxiv 2020;doi:10.1101/2020.06.29.174888; Sci Immunol 2020;5eabd2071]
“Adenovirus-vectored vaccines are known to induce strong cellular immunity and ChAdOx1 nCoV-19 vaccination resulted in marked increases in SARS-CoV-2 spike-specific effector T-cell responses as early as day 7, peaking at day 14 and maintained up to day 56 as expected with adenoviral vectors,” the researchers said. “However, a boost in cellular responses was not observed following the second ChAdOx1 nCoV-19 dose.”
This finding supports that of a previous study on viral vectored vaccines given as part of a homologous prime-boost regimen. [Sci Rep 2018;8:3390]
Phase III trials for ChAdOx1 nCoV-19 are currently in progress in Brazil, South Africa, and the UK.