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.