CanSino Biologic, a company based in Tianjin, China working with a clinical team in Wuhan, report the results of a phase 1 safety trial of an adenovirus vector based SARS-CoV-2 vaccine candidate. The virus vector expressed the entire spike protein, the S gene.
Three groups of healthy volunteers, 36 per group, were administered three escalating doses of the vaccine by intramuscular injection. The volunteers were young, average age 36 (ages-18-60, only 17 of the 108 volunteers were ages 50-60) half male, half female. The vaccinated volunteers were followed for 28 days post inoculation. The primary endpoints were adverse reactions on day 7 and safety at day 28. Immunologic parameters were also assessed.
No serious side effects were noted throughout he study period. Common side effects observed at all doses included muscle pain at the site of injection, headache, fatigue and fever—all transient.
Immune reactions to SARS-Cov-2 were measured at day 14, and 28. Both T cell and antibody responses were observed in all those inoculated. Antibodies for the virus were present at 14 day and “peaked” at 28 days. The antibody titers to the S protein were significant and were higher the vaccine dose. Antibodies to the receptor binding domain were detected in more than 90% of those receiving the high and middle doses and in about one third of those in the low dose group.
The ability of the serum to neutralize a pseudotyped virus carrying the SARS-CoV-2 S protein was also measured. Overall the titer of neutralizing antibodies was low but detectable at day 28.
T cell responses to the viral S protein were also measured. More than 90% of those who received the vaccine made detectable T cell responses to the S protein at the high dose and significant response at the lower doses. All of those vaccinated are reported to have made either detectable T cell responses or neutralizing antibodies to live SARS-CoV-2.
The authors conclude that the vaccine candidate met the initial end points regarding adverse events and safety and provide evidence of immunogenicity against the target protein and for this reason believe further investigation in human trials for safety and preliminary efficacy are justified.
The trial was carefully done and thoughtfully reported. A significant concern is the low titer of neutralizing antibody and poor immune responses for those who had pre-existing anti-adenovirus antibodies. Whether the immune response to the vaccine candidates is sufficiently robust to confer complete or partial protection is open question. The authors also mention that the antibody response in the older cohort, ages 50-60, is less robust that younger volunteers, an additional concern as those in most in need of protection from infection are age 70 and above, a population known to mount poor long term immune responses to to novel infections.
The authors also discuss the need to study the persistence of the anti-S protein antibodies. Short lived immune responses are typically human coronavirus infections.
As the authors state this the first published report of a Covid-19 vaccine candidate in humans.
They are aware, and indeed mention, other trials now in progress, some with similar adenovirus vectors carrying the S gene, others with with whole killed virus or nucleic acid based (both RNA and DNA) vaccine candidates.
It is a pleasure to see this data in a published and reviewed manuscript allowing independent analysis of the primary data. I agree with the conclusion that further human studies with this vaccine candidate are justified, albeit with the caution that the neutralizing titers were far below what is likely to be needed for a vaccine that is even partially protective.