Phase 2 study shows safety and immunogenicity of SARS-CoV-2 recombinant protein vaccine

While the currently available coronavirus disease 2019 (COVID-19) vaccines have shown great efficacy in reducing the risk of hospitalization upon infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the availability of these vaccines is still lacking on a global scale. Further, in certain subpopulations, adolescent boys have demonstrated a higher than the average number of adverse events upon receiving the mRNA vaccine, promoting the continued development of alternative vaccines.

Study: Safety and immunogenicity of a SARS-CoV-2 recombinant protein vaccine with AS03 adjuvant in healthy adults: interim findings from a phase 2, randomised, dose-finding, multi-centre study. Image Credit: ktsdesign/ Shutterstock

In a paper recently uploaded to the preprint server medRxiv*, the results of a phase 2 clinical trial featuring a SARS-CoV-2 recombinant protein vaccine developed by GlaxoSmithKline are reported, demonstrating a favorable immune response amongst both naïve and non-naïve adults with an acceptable safety profile.

How was the study performed?

A baculovirus expression vector system was utilized to recombinantly produce pre-fusion SARS-CoV-2 spike protein antigen, based on wildtype SARS-CoV-2, which was also incorporated with a squalene-based adjuvant termed AS03, also previously used in H1N1 and H5N1 influenza vaccines.

Earlier phase 1 studies had established that this adjuvant provided superior results over AF03 adjuvant. This current phase 2 trial aims to assess the most suitable dose size in a two-dose regimen: 5, 10, or 15 µg of antigen with an equal quantity of adjuvant across groups.

722 Adults aged 18-95 were given two doses of one size intramuscularly with a 21-day interval, and both blood and nasopharyngeal swab samples were collected immediately before each. Additional samples were collected two weeks post-vaccination, and all were tested for the development of neutralizing antibodies against the SARS-CoV-2 beta variant of concern, bearing the D614G mutation.

Samples collected before vaccination were also used to compare the naiveté of each participant to SARS-CoV-2 by analysis of convalescent sera, and it was found that 85.2% had not been previously infected.

Neutralizing antibody titers

Amongst the SARS-CoV-2 naïve neutralizing antibody titers did not rise from baseline following administration of the first dose, then increasing in relation to dose size in younger adults but not those aged over 60, for whom dose size was less influential. An at least four-fold rise in neutralizing antibody titers was observed at 36 days post-vaccination in 97.4-100% and 93.9-96.7% of adults (18-59) and older adults (≥60), respectively.

The antibody response in vaccinated individuals was comparable to that observed in a convalescent sera panel. In contrast, antibody titers in the non-naïve were found to exceed these after only one dose. This is in line with reports of the currently available SARS-CoV-2 vaccines, where seropositive individuals achieve robust antibody titers after a single dose.

Cell-mediated immunity was assessed amongst a subset of participants, and increases in interferon-γ, interleukin-2 (IL-2), and tumor necrosis factor-α cytokines were more robust than seen for IL-4, IL-5, and IL-13. The latter is more heavily involved in mediating the inflammatory pathway in response to allergies, and thus this indicates that the vaccine is eliciting the appropriate immune response.  

Vaccine safety

Participants were asked to keep a diary of adverse events in the weeks following vaccination, with the frequency of reports being similar amongst each dose size group. Younger adults had a slightly higher frequency of adverse events than older adults, around 93% compared to 88%, and adverse events were more frequent after the second dose, around 87% compared to 78%.

Around 20% of participants reported at least one grade 3 event (as defined by the FDA) regardless of age or dose size, with the most commonly reported being injection site pain (~82%) or malaise (~10%), resolved within 48 hours. Grade 1 or 2 adverse events included malaise (~59%), headache (~57%), and myalgia (~55%). Participants receiving the highest dosage of the vaccine reported a 7.9% rate of grade 3 unsolicited adverse events with reactogenicity symptoms, compared to only 2.1% of the low-dose group.

Six high-dose and one low-dose participant reported elevated blood pressure that resolved within 48 hours, with one of the former also experiencing maculopapular rash and headache that persisted for longer.  Similar rates of adverse events were reported for both the naïve and non-naïve, unlike reports from other vaccines where higher rates of adverse events are found amongst seropositive individuals.

*Important notice

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

Written by

Michael Greenwood

Michael graduated from Manchester Metropolitan University with a B.Sc. in Chemistry in 2014, where he majored in organic, inorganic, physical and analytical chemistry. He is currently completing a Ph.D. on the design and production of gold nanoparticles able to act as multimodal anticancer agents, being both drug delivery platforms and radiation dose enhancers.