A two-dose optimum for recombinant S1 protein-based COVID-19 vaccination

Abstract

Background: Recombinant protein subunit vaccination is considered to be a safe, fast and reliable technique when combating emerging and re-emerging diseases such as coronavirus disease 2019 (COVID-19). Typically, such subunit vaccines require the addition of adjuvants to attain adequate immunogenicity. AS01, which contains adjuvants MPL and saponin QS21, is a liposome-based vaccine adjuvant system that is one of the leading candidates. However, the adjuvant effect of AS01 in COVID-19 vaccines is not well described yet.

Methods: In this study, we utilized a mixture of AS01 as the adjuvant for an S1 protein-based COVID-19 vaccine.

Results: The adjuvanted vaccine induced robust immunoglobulin G (IgG) binding antibody and virus-neutralizing antibody responses. Importantly, two doses induced similar levels of IgG binding antibody and neutralizing antibody responses compared with three doses and the antibody responses weakened only slightly over time up to six weeks after immunization.

Conclusion: These results suggested that two doses may be enough for a clinical vaccine strategy design using MPL & QS21 adjuvanted recombinant protein, especially in consideration of the limited production capacity of COVID-19 vaccine in a public health emergency.

Keywords: Adjuvant; COVID-19; Dose optimum; Protein vaccine.

Fig. 1

The optimization of dosage schedule. (A) The vaccination schedule. BALB/c mice were vaccinated intramuscularly with vaccines in groups of six as indicated, then the mice were sacrificed at 2 weeks after the final vaccination for assays of IgG binding antibody and neutralizing antibody responses. (B) The S1-specific antibody responses. (C) The neutralizing antibody titer. Data are shown as mean values (mean ± SD) for each group of six mice.

Fig. 2

Duration of responses after two-dose vaccination. (A) The vaccination schedule. BALB/c mice were vaccinated intramuscularly with vaccines as indicated, then the mice were sacrificed at 2 weeks, 4 weeks, and 6 weeks after the final vaccination for assays of IgG binding antibody and neutralizing antibody responses. (B) S1-specific antibody responses. (C) The virus-neutralizing antibody titer. Data are shown as mean values (mean ± SD) for each group of six mice.