SARS-CoV-2 was declared a pandemic on March 11, 2020 by the World
Health Organization and since then has spread globally to infect
more than 14 million individuals and kill more than 597,000.
Currently, the WHO reports there are 137 vaccine candidates under
preclinical development and 23 in early development.
Replication-deficient viral vectored vaccines, which were previously
used in immunocompromised individuals with no safety concerns, were
used as a vaccine model in this study conducted by the University of
Oxford.
The glycoprotein spikes located on the surface of the enveloped, positive single-stranded RNA viruses known as coronaviruses are responsible for mediation of receptor binding and cell entry during infection. Having a strong role in receptor binding and membrane fusion, the coronaviruses’ spike proteins make it an attractive target for vaccine development. ChAdOx1 MERS, a chimpanzee adenovovirus-vectored vaccine that encodes for the spike protein of the Middle East respiratory syndrome coronavirus (MERS-CoV), was shown to provide protection against non-human primates with a single dose. Data from a phase 1 clinical trial also indicated that ChAdOx1 MERS was safe, well-tolerated, and elicited humoral and cellular responses against MERS-CoV within 1 month of vaccination.
The replication-deficient simian adenovirus vector ChAdOx1, the full-length structural surface spike protein of SARS-COV-2, and a tissue plasminogen activator leader sequence were the main components of the ChAdOx1 nCoV-19 vaccine. In rhesus macaques, the ChAdOx1 nCoV-19 vaccine was able to induce humoral and cellular immune response and offer protection against lower respiratory tract infection with one single dose.
In this study, a phase 1-2 single-blind, randomized controlled trial of the vaccine was compared with a meningococcal group A, C, W-135 and Y conjugate vaccine. The trial was conducted at five centers within the UK. Healthy individuals aged 18-55 were recruited for this study and volunteer participants who presented any history of SARS-CoV-2 infection, had higher risk for SARS-CoV-2 exposure prior to enrollment, or had any onset of fever, cough, shortness of breath, anosmia, or ageusia since Feb 1, 2020 were excluded from the trial. Randomization was used to administer the ChAdOx1 nCoV-19 vaccine or the meningococcal vaccine (MenACWY) 1:1. MenACWY was used for comparison in participants of local or systemic reactions.
In two of the five trial sites where this study was conducted, prophylactic paracetamol was allowed as a protocol amendment before vaccination to reduce vaccine-associated reaction. Based on administration vaccine ChAdOx1 MERS, a dose of 5 x 1010 viral particles were chosen and given to participants.
Despite a higher reactogenicity profile than MenACWY (control vaccine), ChAdOx1 nCoV-19 vaccine was safe and tolerated when given as a single dose. There were no serious adverse events reported, and any adverse events were mild or moderate. By Day 28, spike-specific antibodies increased and neutralizing antibodies were observed after a booster dose. Neutralizing antibodies were further increased by a second dose. The study proposed that if neutralizing antibodies were shown to be an indicator of protection in humans due to correlation of neutralization assays with IgG quantification, a standardized ELISA may be sufficient to predict protection. Research in this study also demonstrated the importance of T-cell response in COVID-19 mitigation. Asymptomatic individuals who were exposed to the virus developed a strong memory T-Cell response.
Due to the susceptibility of older individuals, the study aims to further explore vaccine administration to individuals in this demographic. Anti-vector antibodies on homologous boosting and the potential of boosting antibody response to SARS-CoV-2 spike protein. In addition to this population, the study proposes to diversify its demographic further by including older age groups with comorbidities, health-care workers, and those at higher risk for exposure of SARS-CoV-2 to assess efficacy, safety, and immunogenicity of the vaccine given as a single dose or two dose administration. The trials are now moving forward, with Phase 3 currently in progress in Brazil, South Africa, and the UK.
