- Phase 1/2, participant blinded, multicentre, randomised, controlled trial--Took place across 5 centres in the UK
- Participants were 18-55 years old and recruited through local advertisements--Underwent screening (medical history, blood test, urine test, and including COVID-19 screening) to ensure participants didn’t have other medical conditions


Study design and participants

- Clinical investigators and laboratory team were blinded to group allocation
- Using block randomisation (block sizes=2 and 4) stratified by study group and study site, “participants were randomly assigned (1:1) to receive either the ChAdOx1 nCoV-19 vaccine or the MenACWY vaccine”--The MenACWY vaccine was used as a placebo to induce the same local systemic reactions which are often associated with viral vector vaccines, maintaining blinding


Randomisation and masking

- Primary outcome was to see the confirmed COVID-19 cases that were symptomatic virologically to able to use the developing vaccine  & test the safety of the vaccine to see if there were any serious harmful effects

- Secondary outcomes include the safety, reactogenicity, and immunogenicity 
of ChAdOx1 nCoV-19



Outcomes

In a Phase 1/2 trial conducted between April 23 and May 21, 2020, participants were assigned to receive either the ChAdOx1 nCoV-19 or the MenACWY vaccine. A subset of participants (56 in the ChAdOx1 nCoV-19 group and 57 in the MenACWY group) took paracetamol. Participants who did not take paracetamol in both groups reported mild to moderate pain after vaccination. The use of paracetamol mitigated these local reactions: 50% of those receiving the ChAdOx1 nCoV-19 vaccine with paracetamol and 32% of those receiving the MenACWY vaccine with paracetamol reported less pain. Furthermore, less tenderness was reported in the groups taking paracetamol compared to those who did not.

ChAdOx1 nCoV-19 Phase 1/2 Trial Results: Paracetamol Effects on Pain and Tenderness

In the phase 1/2 trial, the ChAdOx1 nCoV-19 vaccine (a chimpanzee adenovirus vector) was administered as a single intramuscular injection to the deltoid area at a dose of $$ 5 	imes 10^{10} $$ viral particles. Participants were recruited into four groups, with blood drawn from all of them:
- Group 1: Received the vaccine only, with early follow-up visits.
- Group 2: Had higher blood volumes drawn to assess humoral and cellular immunogenicity.
- Group 3: Consisted of 10 participants who received a booster after the first dose, with follow-ups similar to Group 1.

Additionally, paracetamol was administered at two out of the five trial sites before and after vaccination to manage vaccine-associated reactions.

Procedures for the ChAdOx1 nCoV-19 Phase 1/2 Trial

- Study design and participants
- Randomisation and masking
- Procedures
- Outcomes
- Results

Smith College

San Jose State University

- ChAdOx1  are a desirable platform of vaccine because they are immunogenic in older adults and can be manufactured at large scale
- Vaccines made by combining adenoviral vectors, DNA, and poxviral vectors have been used in an attempt to improve immunogenicity--Emergence of antivector immunity inhibits the potency of a second dose, so homologous adenoviral regimens are typically avoided
- "The ChAdOx1 nCoV-19 vaccine (AZD1222) consists of the replication-deficient simian adenovirus vector ChAdOx1, containing the full-length structural surface glycoprotein (spike protein) of SARS-CoV-2, with a tissue plasminogen activator leader sequence. ChAdOx1 nCoV-19 expresses a codon-optimised coding sequence for the spike  protein (GenBank accession number MN908947)."

ChAdOx1 nCoV-19 vaccine by The University of Oxford

Folegatti, Pedro  M. “Safety and Immunogenicity of the ChAdOx1 NCoV-19 Vaccine against SARS-CoV-2: a Preliminary Report of a Phase 1/2, Single-Blind, Randomised Controlled Trial.” The Lancet, vol. 396, no. 10249, 15 Aug. 2020, pp. 467–478., www.sciencedirect.com/science/article/pii/S0140673620316044. 

Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial

- ChAdOx1 nCoV-19 is a viral vector vaccine which has been tested against small animals with varying success. T-Cell responses have been higher in pigs 42 days in rather than 14 days, and one dose of this vaccine elicits an antibody response.
- In chimpanzies, vaccines of ChAdOx1 MERS were given to prrevent MERS-CoV. The vaccine was safe, well tolerated, and chimpanizes showed an enhanced immune response to MERS-CoV within 1 months of vaccination.

ChAdOx1 nCoV-19 Animal Trials

Methods of Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial

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