Immunological Study of Combined Administration of SARS-CoV-2 DNA Vaccine and Inactivated Vaccine

Abstract

Objective: We constructed two DNA vaccines containing the receptor-binding domain (RBD) genes of multiple SARS-CoV-2 variants and used them in combination with inactivated vaccines in a variety of different protocols to explore potential novel immunization strategies against SARS-CoV-2 variants. Methods: Two DNA vaccine candidates with different signal peptides (namely, secreted and membrane signal peptides) and RBD protein genes of different SARS-CoV-2 strains (Wuhan-Hu-1, B.1.351, B.1.617.2, C.37) were used. Four different combinations of DNA and inactivated vaccines were tested, namely, Group A: three doses of DNA vaccine; B: three doses of DNA vaccine and one dose of inactivated vaccine; C: two doses of inactivated vaccine and one dose of DNA vaccine; and D: coadministration of DNA and inactivated vaccines in two doses. Subgroups were grouped according to the signal peptide used (subgroup 1 contained secreted signal peptides, and subgroup 2 contained membrane signal peptides). The in vitro expression of the DNA vaccines, the humoral and cellular immunity responses of the immunized mice, the immune cell population changes in local lymph nodes, and proinflammatory cytokine levels in serum samples were evaluated. Results: The antibody responses and cellular immunity in Group A were weak for all SARS-CoV-2 strains; for Group B, there was a great enhancement of neutralizing antibody (Nab) titers against the B.1.617.2 variant strain. Group C showed a significant increase in antibody responses (NAb titers against the Wuhan-Hu-1 strain were 768 and 1154 for Group C1 and Group C2, respectively, versus 576) and cellular immune responses, especially for variant B.1.617.2 (3240 (p < 0.001) and 2430 (p < 0.05) for Group C1 and Group C2, versus 450); Group D showed an improvement in immunogenicity. Group C induced higher levels of multiple cytokines. Conclusion: The DNA vaccine candidates we constructed, administered as boosters, could enhance the humoral and cellular immune responses of inactivated vaccines against COVID-19, especially for B.1.617.2.

Immunogenicity of novel DNA vaccines encoding receptor‐binding domain (RBD) dimer‐Fc fusing antigens derived from different SARS‐CoV‐2 variants of concern

“…DNA vaccines have aroused many interests as multiple vaccine candidates for cancer therapy entered clinical trials, which proved that DNA vaccines were well tolerated and capable of inducing immune responses in humans 33 . Since the outbreak of the COVID‐19 epidemic, a number of SARS‐CoV‐2 DNA vaccines have been reported, 23,24,34–42 among which the ZyCoV‐D vaccine was the first to be licensed. Improving the immunogenicity is one of the key issues in the development of DNA vaccines.…”

“…immune responses in humans. 33 Since the outbreak of the COVID-19 epidemic, a number of SARS-CoV-2 DNA vaccines have been reported, 23,24,[34][35][36][37][38][39][40][41][42] among which the ZyCoV-D vaccine was the first to be licensed. Improving the immunogenicity is one of the key issues in the development of DNA vaccines.…”

Poor immune response to coronavirus disease vaccines in decompensated cirrhosis patients and liver transplant recipients

“…Inactivated vaccines stimulate antibody-mediated immune responses, which have a shorter lifespan with weak immunogenicity. [26] , [27] Inactivated viral vaccines induce low cytotoxic CD8+ cells, which are required for effective immune responses and greater and longer immunogenicity. [28] Though inactivated vaccines are safer than live attenuated vaccines, the immunogenic epitopes may deform structurally during the inactivation process, destabilizing the protection that must be delivered.…”

A survey of mechanisms underlying current and potential COVID‐19 vaccines

“…Neutralizing titers were at least equal to or higher than the titers measured after the homologous prime boost approach with viral vectors [113]. Preclinical studies also point to the possibility of combining inactivated vaccine prime with DNA boosting [114]. While the abovementioned studies are merely representative of various attempts to combine relevant vaccine modalities, they do illustrate the feasibility and relevance, when we think about how to best cope with SARS‐CoV‐2 in the long‐term.…”