Single-injection COVID-19 subunit vaccine elicits potent immune responses

Xiaoyong Zhou; Haozheng Wang; Ying Luo; Lei Cui; Ying Guan; Yongjun Zhang

doi:10.1016/j.actbio.2022.08.006

Single-injection COVID-19 subunit vaccine elicits potent immune responses

Acta Biomater. 2022 Oct 1:151:491-500. doi: 10.1016/j.actbio.2022.08.006. Epub 2022 Aug 7.

Authors

Xiaoyong Zhou¹, Haozheng Wang¹, Ying Luo², Lei Cui¹, Ying Guan³, Yongjun Zhang⁴

Affiliations

¹ Key Laboratory of Functional Polymer Materials and State Key Laboratory of Medicinal Chemical Biology, Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China.
² School of Chemistry, Tiangong University, Tianjin 300387, China.
³ Key Laboratory of Functional Polymer Materials and State Key Laboratory of Medicinal Chemical Biology, Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China. Electronic address: yingguan@nankai.edu.cn.
⁴ Key Laboratory of Functional Polymer Materials and State Key Laboratory of Medicinal Chemical Biology, Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China; School of Chemistry, Tiangong University, Tianjin 300387, China. Electronic address: yongjunzhang@nankai.edu.cn.

Abstract

Current vaccination schedules, including COVID-19 vaccines, require multiple doses to be administered. Single injection vaccines eliciting equivalent immune response are highly desirable. Unfortunately because unconventional release kinetics are difficult to achieve it still remains a huge challenge. Herein a single-injection COVID-19 vaccine was designed using a highly programmable release system based on dynamic layer-by-layer (LBL) films. The antigen, S1 subunit of SARS-CoV-2 spike protein, was loaded in CaCO₃ microspheres, which were further coated with tannic acid (TA)/polyethylene glycol (PEG) LBL films. The single-injection vaccine was obtained by mixing the microspheres coated with different thickness of TA/PEG films. Because of the unique constant-rate erosion behavior of the TA/PEG coatings, this system allows for distinct multiple pulsatile release of antigen, closely mimicking the release profile of antigen in conventional multiple dose vaccines. Immunization with the single injection vaccine induces potent and persistent S1-specific humoral and cellular immune responses in mice. The sera from the vaccinated animal exhibit robust in vitro viral neutralization ability. More importantly, the immune response and viral inhibition induced by the single injection vaccine are as strong as that induced by the corresponding multiple dose vaccine, because they share the same antigen release profile. STATEMENT OF SIGNIFICANCE: Vaccines are the most powerful and cost-effective weapons against infectious diseases such as COVID-19. However, current vaccination schedules, including the COVID-19 vaccines, require multiple doses to be administered. Herein a single-injection COVID-19 vaccine is designed using a highly programmable release system. This vaccine releases antigens in a pulsatile manner, closely mimicking the release pattern of antigens in conventional multiple dose vaccines. As a result, one single injection of the new vaccine induces an immune response and viral inhibition similar to that induced by the corresponding multiple-dose vaccine approach.

Keywords: COVID-19 vaccines; Pulsatile release; Single-injection vaccines; Unconventional release kinetics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
COVID-19 Vaccines
COVID-19* / prevention & control
Humans
Immunity
Mice
Polyethylene Glycols
SARS-CoV-2
Spike Glycoprotein, Coronavirus
Tannins
Vaccines, Subunit
Viral Vaccines*

Substances

COVID-19 Vaccines
Spike Glycoprotein, Coronavirus
Tannins
Vaccines, Subunit
Viral Vaccines
spike protein, SARS-CoV-2
Polyethylene Glycols