What is the mechanism of action of Covishield (ChAdOx1 nCoV-19) vaccine?

Mechanism of Action of Covishield (ChAdOx1 nCoV-19) Vaccine

Covishield (ChAdOx1 nCoV-19) vaccine uses a replication-deficient chimpanzee adenovirus vector to deliver the full-length SARS-CoV-2 spike protein DNA sequence into host cells, triggering both humoral and cellular immune responses against the virus. 1

Core Mechanism

• Covishield utilizes a recombinant, replication-deficient chimpanzee adenovirus vector (ChAdOx1) that encodes the SARS-CoV-2 spike glycoprotein 1
• Unlike mRNA vaccines, this adenovirus vector-based vaccine delivers the DNA sequence of the spike protein rather than mRNA 1
• After intramuscular injection, the adenovirus vector enters host cells where the DNA is transcribed into mRNA, which is then translated to produce the SARS-CoV-2 spike protein 2
• The expressed spike protein appears on the cell surface, where it is recognized by the immune system as a foreign antigen 2
• Since the adenovirus vector is replication-deficient, it cannot cause infection or disease 1

Immune Response Generated

• The vaccine induces both humoral (antibody) and cellular immune responses against the spike protein 2, 3
• Spike-specific T-cell responses typically peak around day 14 post-vaccination 2
• Anti-spike IgG antibodies rise by day 28 and are significantly boosted following a second dose 2
• The immune response is predominantly mediated by type-1 T helper cells, as demonstrated by IgG subclass profiling and cytokine expression 3
• Neutralizing antibodies against SARS-CoV-2 are detected in 91-100% of participants after a single dose, with all participants showing neutralizing activity after a booster dose 2

Efficacy and Protection

• In clinical trials, Covishield demonstrated approximately 90% effectiveness against symptomatic COVID-19 4
• Animal studies showed significantly reduced viral load in the bronchoalveolar lavage fluid and lower respiratory tract tissue of vaccinated rhesus macaques challenged with SARS-CoV-2 3
• The vaccine prevented pneumonia in vaccinated SARS-CoV-2-infected animals, though it did not prevent nasal shedding 3
• Importantly, no evidence of immune-enhanced disease was observed after viral challenge in vaccinated animals 3

Safety Considerations

• As the vaccine does not contain live virus but rather a replication-deficient vector, it cannot cause COVID-19 infection 1
• Local and systemic reactions are common but typically mild and transient, including pain at injection site, feeling feverish, chills, muscle ache, headache, and malaise 2
• Many of these reactions can be reduced by prophylactic paracetamol 2
• Rare adverse events like facial angioedema have been reported but are uncommon 5

Comparison with Other COVID-19 Vaccines

• Unlike mRNA vaccines (e.g., Pfizer-BioNTech) that deliver mRNA encoding the spike protein encapsulated in lipid nanoparticles, Covishield uses an adenovirus vector to deliver DNA encoding the spike protein 6
• Both approaches result in the production of the SARS-CoV-2 spike protein by host cells, but through different delivery mechanisms 6, 2
• The efficacy of adenovirus vector vaccines like Covishield may potentially be reduced if significant mutations occur in the spike protein structure 4

Clinical Applications

• Covishield has been widely used in vaccination campaigns globally, including as part of the UK's national vaccination program 1
• It is administered as an intramuscular injection, typically in a two-dose regimen 2
• The vaccine has demonstrated safety and efficacy in all adult age groups, including both healthy individuals and patients at risk of severe COVID-19 1