Experimental Vaccines Show Promise Against COVID-19 in Healthy Subjects

Two experimental vaccines, one from AstraZeneca and the other from CanSino Biologics, have shown promising results against coronavirus disease 2019 (COVID-19) in a phase 1/2 trial and a phase 2 trial. Results for both were published in The Lancet.

The interim results of AstraZeneca’s phase 1/2 COV001 trial of AZD1222 showed that the vaccine was tolerated and generated robust immune responses against the virus in all participants who were evaluated.¹

While there are no vaccines currently approved to prevent COVID-19, which is caused by severe acute respiratory syndrome coronavirus 2 (SAR-CoV-2), there are more than 137 candidates undergoing preclinical development and 23 in early clinical development, the authors noted.

“An ideal vaccine against SARS-CoV-2 would be effective after one or two vaccinations; would protect target populations such as older adults and those with comorbidities, including immunocompromised individuals; would confer protection for a minimum of 6 months; and would reduce onward transmission of the virus to contacts,” they explained.

AZD1222 is being tested in a trial of 1077 healthy adults in the United Kingdom between the ages of 18 and 55. The vaccine (n = 543) is being assessed against a meningococcal conjugate vaccine, MenACWY (n = 534).

A single dose of the vaccine elicited a spike in antibodies by day 28 with neutralizing antibody responses detected in 91% of patients. After a booster dose, all participants had neutralizing activity. The vaccine also showed increases in T-cell responses as early as day 7 and these responses were maintained for 56 days.

“The immune responses observed following vaccination are in line with what we expect will be associated with protection against the SARS-CoV-2 virus, although we must continue with our rigorous clinical trial programme to confirm this,” Andrew J. Pollard, PhD, coauthor of the study, said in a statement. “We saw the strongest immune response in participants who received two doses of the vaccine, indicating that this might be a good strategy for vaccination.”

Phase 3 trials of the vaccine are underway in Brazil, South Africa, and the United Kingdom.

In CanSino Biologics’s phase 2 trial, 508 healthy adults age 18 and older participated and were randomly assigned to receive either the Ad5-vectored vaccine (1 × 10¹¹ viral particles, n = 253; 5 × 10¹⁰ viral particles, n = 129) or placebo (n = 126).²

Both doses of the vaccine induced significant neutralizing antibody responses. Among patients in the 1 × 10¹¹ viral particles dose group, 95% showed either cellular or humoral immune responses at day 28 post vaccination compared with 91% of participants in the 5 × 10¹⁰ viral particles dose group.

“Increasing age and high pre-existing anti-Ad5 immunity were found to be able to significantly reduce the immune responses to the vaccine,” according to the authors. “In some participants with high pre-existing anti-Ad5 immunity, one injection of the vaccine might be inadequate to induce a high level of humoral immune responses, particularly for people aged 55 years or older.”

References

1. Folegatti PM, Ewer KJ, Aley PK, et al, on behalf of the Oxford COVID Vaccine Trial Group. 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. Lancet. Published online July 20, 2020. doi:10.1016/S0140-6736(20)31604-4

2. Zhu F-C, Guan X-H, Li-Y-H, et al. 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. Published online July 20, 2020. doi:10.1016/S0140-6736(20)31605-6