Lipid-Based Poly(I:C) Adjuvants Strongly Enhance the Immunogenicity of SARS-CoV-2 Receptor-Binding Domain Vaccine
| Title: | Lipid-Based Poly(I:C) Adjuvants Strongly Enhance the Immunogenicity of SARS-CoV-2 Receptor-Binding Domain Vaccine |
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| Authors: | Yixin Wu, Liuxian Meng, Huicong Zhang, Shun Hu, Fusheng Li, Yingjie Yu |
| Source: | Infectious Diseases & Immunity, Vol 3, Iss 1, Pp 3-12 (2023) |
| Publisher Information: | Wolters Kluwer Health - Lippincott Williams Wilkins, 2023. |
| Publication Year: | 2023 |
| Collection: | LCC:Infectious and parasitic diseases |
| Subject Terms: | Infectious and parasitic diseases, RC109-216 |
| More Details: | Abstract. Background. The outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has greatly threatened public health. Recent studies have revealed that the spike receptor-binding domain (RBD) of SARS-CoV-2 is a potent target for vaccine development. However, adjuvants are usually required to strengthen the immunogenicity of recombinant antigens. Different types of adjuvants can elicit different immune responses. Methods. We developed an RBD recombinant protein vaccine with a polyriboinosinic acid–polyribocytidylic acid [poly(I:C)] adjuvant to evoke a strong immune response. The delivery of poly(I:C) was optimized in two steps. First, poly(I:C) was complexed with a cationic polymer, poly-l-lysine (PLL), to form poly(I:C)–PLL, a polyplex core. Thereafter, it was loaded into five different lipid shells (group II, III-1,2-distearoyl-sn-glycero-3-phosphocholine [DSPC], III-1,2-dioleoyl-sn-glycero-3-phosphoethanolamine [DOPE], IV-DOPE, and IV-DSPC). We performed an enzyme-linked immunosorbent assay and enzyme-linked immunosorbent spot assay to compare the ability of the five lipopolyplex adjuvants to enhance the immunogenicity of the SARS-CoV-2 RBD protein, including humoral and cellular immune responses. Finally, the adjuvant with the highest immunogenicity was selected to verify the protective immunity of the vaccine through animal challenge experiments. Results. Recombinant RBD protein has low immunogenicity. The different adjuvants we developed enhanced the immunogenicity of the RBD protein in different ways. Among the lipopolyplexes, those containing DOPE (III-DOPE and IV-DOPE) elicited RBD-specific immunoglobulin G antibody responses, and adjuvants with four components elicited better RBD-specific immunoglobulin G antibody responses than those containing three components (P < 0.05). The IC50 and IC90 titers indicated that the IV-DOPE lipopolyplex had the greatest neutralization ability, with IC50 titers of 1/117,490. Furthermore, in the challenge study, IV-DOPE lipopolyplex protected mice from SARS-CoV-2 infection. On the fourth day after infection, the average animal body weights were reduced by 18.56% (24.164 ± 0.665 g vs. 19.678 ± 0.455 g) and 0.06% (24.249 ± 0.683 g vs. 24.235 ± 0.681 g) in the MOCK and vaccine groups, respectively. In addition, the relative expression of viral RNA in the vaccinated group was significantly lower than that in the MOCK group (P < 0.05). Interstitial inflammatory cell infiltration was observed in the MOCK group, whereas no obvious damage was observed in the vaccinated group. Conclusions. The IV-DOPE–adjuvanted SARS-CoV-2 recombinant RBD protein vaccine efficiently protected mice from SARS-CoV-2 in the animal challenge study. Therefore, IV-DOPE is considered an exceptional adjuvant for SARS-CoV-2 recombinant RBD protein-based vaccines and has the potential to be further developed into a SARS-CoV-2 recombinant RBD protein-based vaccine. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 2096-9511 2693-8839 00000000 |
| Relation: | http://journals.lww.com/10.1097/ID9.0000000000000074; https://doaj.org/toc/2096-9511; https://doaj.org/toc/2693-8839 |
| DOI: | 10.1097/ID9.0000000000000074 |
| Access URL: | https://doaj.org/article/ecc0bb80e04e416aaec9fff199097f4d |
| Accession Number: | edsdoj.0bb80e04e416aaec9fff199097f4d |
| Database: | Directory of Open Access Journals |
| ISSN: | 20969511 26938839 00000000 |
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| DOI: | 10.1097/ID9.0000000000000074 |
| Published in: | Infectious Diseases & Immunity |
| Language: | English |