While the currently available vaccines against coronavirus disease 2019 (COVID-19) have shown great efficacy in reducing the risk of hospitalization in case of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), these vaccines are still lacking on a global scale. . In addition, young boys in certain subpopulations have shown a higher than average side effect of receiving the mRNA vaccine, which promotes the continued development of alternative vaccines.
Study: Safety and immunogenicity of a SARS-CoV-2 recombinant protein vaccine with AS03 adjuvant in healthy adults: preliminary findings from a phase 2, randomized, dose-finding, multi-center study. Image credit: ktsdesign / Shutterstock
In a paper recently uploaded to the pre-print server medRxiv*, reports the results of a Phase 2 clinical trial with a SARS-CoV-2 recombinant protein vaccine developed by GlaxoSmithKline, showing a favorable immune response among both naive and non-naïve adults with an acceptable safety profile.
How was the survey conducted?
A baculovirus expression vector system was used to recombinantly produce pre-fusion SARS-CoV-2 spike protein antigen, based on wild-type SARS-CoV-2, which was also incorporated with a squalene-based adjuvant designated AS03, also previously used in H1N1 and H5N1 influenza vaccines .
Previous phase 1 studies had established that this adjuvant gave superior results over AF03 adjuvant. This current Phase 2 study aims to assess the most appropriate dose size in a two-dose regimen: 5, 10 or 15 antg of antigen with an equal amount of adjuvant across groups.
722 adults aged 18-95 received two doses of one size intramuscularly with a 21-day interval, and both blood and nasopharyngeal swab specimens were collected immediately before each. Additional samples were collected two weeks after vaccination, and all were tested for the development of neutralizing antibodies to the SARS-CoV-2 beta variant of concern carrying the D614G mutation.
Samples collected before vaccination were also used to compare each participant’s naivety with SARS-CoV-2 by analysis of convalescent sera, and it was found that 85.2% had not been previously infected.
Neutralizing antibody titers
Among the SARS-CoV-2-naïve neutralizing antibody titers did not increase from baseline after first dose administration and then increased relative to dose size in younger adults, but not those over 60 years of age for whom the dose size was less influential. An at least four-fold increase in neutralizing antibody titers was observed 36 days after 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 serapanel. 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, in which seropositive individuals achieve robust antibody titers after a single dose.
Cell-mediated immunity was assessed among 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 strongly involved in mediating the inflammatory pathway in response to allergy, thus indicating that the vaccine elicits the appropriate immune response.
Participants were asked to keep a diary of side effects in the weeks after vaccination, with the frequency of reports being the same for each dose size group. Younger adults had a slightly higher incidence of side effects than older adults, about 93% versus 88%, and side effects were more frequent after the second dose, about 87% versus 78%.
About 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 side effects included malaise (~ 59%), headache (~ 57%) and myalgia (~ 55%). Participants who received the highest dose of the vaccine reported a 7.9% degree of adverse reactions of grade 3 with reactogenicity symptoms compared to only 2.1% of the low-dose group.
Six high-dose and one low-dose participant reported high blood pressure that disappeared within 48 hours, with one of the former also experiencing maculopapular rash and headaches that persisted for extended periods of time. Similar frequencies of adverse reactions were reported for both the naive and non-naïve, in contrast to reports from other vaccines where there are higher adverse reactions among seropositive individuals.
medRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered as crucial, guide clinical practice / health-related behavior or be treated as established information.
- Sridhar, S. et al. (2021) “Safety and immunogenicity of a SARS-CoV-2 recombinant protein vaccine with AS03 adjuvant in healthy adults: preliminary findings from a phase 2, randomized, dose-finding, multi-center study”. medRxiv. doi: 10.1101 / 2021.10.08.21264302.