- In some people with high pre-existing immunity, the dosage Zhu and colleagues determined to be more safe, (5.0X10^10 viral particles) may not be strong enough to induce an immune response
- Older people are more likely to have been exposed to Ad5, and therefore are more likely to tolerate a higher dosage of the vaccine than younger people who have not been previously exposed to Ad5. 
- From the researchers’ previous experience with the Ad5 vector based Ebola vaccine, they found that an additional dose 3 to 6 months after the primary dose may be a good solution for anti-Ad5 immunity. 


Addressing Anti-Ad5 immunity in the Ad5 vectored COVID-19 Vaccine 

- The vaccine dosages were chosen based on the results from the phase 1 trial 
- In phase 1, most of the adverse reactions were within the group that was administered 1.5X10^11 viral particles, so Zhu and colleagues decided to test 1.0X10^11 and 5.0X10^10 viral particles
- It was expected that 1.0X10^11 viral particles would be the better dosage of the two doses tested because an increased antigen dose is usually associated with better immunogenicity. However, that was not the case.
- It was found that 5.0x10^10 is the better of the two doses-less adverse effects and comparable immunogenicity

Vaccine Dosages in the Phase 2 Trial of the Ad5 Vector-based COVID-19 Vaccine


- Post Vaccination Reactions 
- Vaccine Dosages 
- Addressing Anti-Ad5 Immunity 


Santa Clara University

Aimed to further assess the immunogencity and safety of Ad5-vectored COVID-19 vaccine in a larger population with only the 5 x 10^10 and 1 x 10^11 viral particles doses after the first-in-human phase 1 trial with CanSino Biologics (Tianjin, China) suggested high-dose vaccine was associated with a higher risk of severe adverse effects. 
- methods
- results
- discussions
- limitations and future work

Study on immunogenicity and safety of Ad5-vectored COVID-19 vaccine in larger population

Zhu FC, Guan XH, Li YH, Huang JY, Jiang T, Hou LH, Li JX, Yang BF, Wang L, Wang WJ, Wu SP, Wang Z, Wu XH, Xu JJ, Zhang Z, Jia SY, Wang BS, Hu Y, Liu JJ, Zhang J, Qian XA, Li Q, Pan HX, Jiang HD, Deng P, Gou JB, Wang XW, Wang XH, Chen W. Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet. doi: 10.1016/S0140-6736(20)31605-6.

https://reader.elsevier.com/reader/sd/pii/S0140673620316056?token=97B865EF00C0E8CED18EB943DA8BC3625887370F6AD86C661591D78080B9D0ADF7A2E0703365A9D821BE21A8F2E5D70E

Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older: a randomised, double-blind, placebo-controlled, phase 2 trial

- location:

single center in Wuhan, China

- participation eligibility: 

age: 18 years or older, HIV-negative, previous SARS-CoV-2 infection-free, axillary temp: 37.0 deg C or less, BMI: 18.5-30.0, general good health, no pregnant/breastfeeding women, no people with mental disease, allergies, cardiovascular disease, other chronic illnesses

- randomized, double-blinded, placebo-controlled

1 x 10^11, 5x10^10 viral particles per mL, placebo were randomized at 2:1:1 ratio

- procedure:

single injection, IM, arm, participants monitored (blood samples collected for antibody responses) for 30 mins, follow-up within 14 days, 28 days, and 6 months, self-reported serious effects, detection limit for RBD = 1:40, for neutralizing antibody to live SARS-CoV-2 virus and a pesudovirus = 1:8 and 1:10, respectively, expression of IFN detected by enzyme-linked immunospot (ELISpot) assay

(see children nodes for more information)

Methods - Study on immunogenicity and safety of Ad5-vectored COVID-19 vaccine in larger population

- Specific antibody responses to RBD and neutralizing antibodies to live SARS-CoV-2 and pseudovirus
- Specific T-cell responses
- Adverse reactions by time


Results - Study on immunogenicity and safety of Ad5-vectored COVID-19 vaccine in larger population

- Limited sample size 
- limited participant geographic diversity
- age of participants (no children included in the trial)
- Short time-period to observe effects of the vaccination (only 28 days)
- No possible analysis of risk of ADE because none of the participants were exposed to SARS-CoV-2 post vaccination. 

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