Candidate for SARS-CoV-2 spike-based vaccine demonstrates high safety and efficacy in a phase I trial

Many vaccines are being tested against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the envelope virus that causes the current coronavirus disease pandemic 2019 (COVID-19).

There is an urgent need for newer and more effective vaccines due to the rapid emergence of highly transmissible and perhaps more virulent lineages of viruses that often give an immune escape. With this observation, it is important that global immunization lasts for months, if not years.

During that time, hundreds of thousands of severe cases of COVID-19 will need to be treated, making the new vaccines a priority to prevent health services from overcoming.

New research paper on preprint published on medRxiv* The server reports the results of the first human trial of the SARS-CoV-2 MVC-COV1901 prefusion-stabilized vaccine in Taiwan.

Stabilized vaccine design

The vaccine must use the immunogenic antigen in the correct conformation to elicit a protective neutralizing response.

In the present case, SARS-CoV-2 mediates binding to the host cell via a receptor called the angiotensin 2 converter enzyme (ACE2) by the spike protein.

Neutralizing antibodies to this virus often block the binding of ACE2-spike to prevent infection. The spike has a state of prefusion and postfusion. To stabilize in the prefusion state, a pair of proline residues is added to obtain S-2P – stabilized prefusion S ectodomain protein class.

This recombinant protein also has a GSAS substitution that eliminates the furin cleavage site at the S1 / S2 interface and a trimerization motif at the C4 end.

Cryoelectron microscopy shows that it is in a prefusion state and is capable of binding ACE2.

The MVC-COV1901 vaccine was formulated with the aid of CpG 1018 and aluminum hydroxide. The first acts as a Toll-like receptor 9, to increase the immune response after exposure, while inducing a Th1 distorted immune response.

Study details

The phase I study MVC-COV1901 included 45 healthy adults between the ages of 20 and 49, who received two doses each, but in high, medium, and low doses. The interval between the two doses was 28 days.

The study found that all three dose groups had the same frequency of mild side effects. No subjects reported fever. One patient had fatigue and a feeling of ill health.

The antibody titer of specific immunoglobulin G (IgG) was significantly increased after the increased dose, with peak geometric mean titers (GMT) to 7,000 for the low-dose group, 7.7,000 for the medium dose, and 11,000 for the high-dose group.

Mean GMTs were similar to those in the set of convalescent serum samples. Seroconversion occurred in all high- and medium-dose vaccine recipients by day 57. The serum of participants in these groups showed neutralizing activity, except in the low-dose group.

Here, too, GMTs were similar to convalescent serum samples, at 52,000 and 82,000, respectively, in the medium- and high-dose groups.

What are the implications?

The study thus shows that MVC-COV1901, a stabilized adjuvant prefusion-based vaccine, is safe, well tolerated, and immunogenic in healthy adults up to 49 years of age. Since the baseline neutralization response is zero in all groups, this confirms the fact that SARS-CoV-2 is not currently transmitted to Taiwan, where the study was conducted.

Complete seroconversion was observed in all recipients of medium and high doses of the vaccine. IgG titers correlated with neutralizing activity against wild-type virus.

Further research will be needed to understand how this translates to protection against infection. However, previous research on other viruses has shown that serum neutralizing activity is a biomarker of a protective antibody response.

Preclinical studies in hamsters have shown the ability of this vaccine candidate to protect against SARS-CoV-2 after two doses. Moreover, GMTs are similar to the mean GMTs of convalescent serum panels.

Further monitoring of humoral immunity will continue until six months have elapsed. The trial is now in Phase 2, involving 3,700 participants, some of whom are older adults and / or have pre-existing diseases, both of which increase the risk for COVID-19.

* Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be considered definitive, guide clinical practice / health-related behavior, or treat it as established information.