A universal
            <scp>SARS‐CoV DNA</scp>
            vaccine inducing highly cross‐reactive neutralizing antibodies and T cells

Appelberg, Sofia; Ahlén, Gustaf; Yan, Jingyi; Nikouyan, Negin; Weber, Sofie; Larsson, Olivia; Höglund, Urban; Aleman, Soo; Weber, Friedemann; Perlhamre, Emma; Apro, Johanna; Gidlund, Eva‐Karin; Tuvesson, Ola; Salati, Simona; Cadossi, Matteo; Tegel, Hanna; Hober, Sophia; Frelin, Lars; Mirazimi, Alì; Sällberg, Matti

doi:10.15252/emmm.202215821

Cited by 14 publications

(18 citation statements)

References 42 publications

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“…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.…”

Section: F I G U R E 4 (See Caption On Next Page)mentioning

confidence: 99%

“…The reported nucleic acid vaccines encoding RBD‐based antigens were focused on monomeric RBD or RBD fusion proteins, including mRNA 21 and DNA 22,23 vaccines expressing secreted form of RBD, and DNA vaccines harboring RBDs of different variants 24 or RBD‐immunostimulator fusing antigen 25 . These vaccines effectively elicited specific humoral and cellular immune responses, either administered solely or in combination with protein vaccines 21–25 . DNA vaccines have the advantages of good safety and stability, short construction period, and low production and transportation costs.…”

Section: Introductionmentioning

confidence: 99%

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

Zhang

Wang

Yang

et al. 2023

Journal of Medical Virology

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The continuously emerging of severe acute respiratory syndrome coronavirus‐2 variants of concern (VOCs) led to a decline in effectiveness of the first‐generation vaccines. Therefore, optimized vaccines and vaccination strategies, which show advantages in protecting against VOCs, are urgently needed. Here we constructed an optimized DNA vaccine plasmid containing built‐in CpG adjuvant, and designed vaccine candidates encoding five forms of antigens derived from Wuhan‐Hu‐1. The results showed that plasmid with receptor binding domain (RBD) dimer‐Fc fusing antigen (2RBD‐Fc) induced the highest level of RBD‐specific IgG and neutralizing antibodies in mice. Then 2dRBD‐Fc and 2omRBD‐Fc vaccines, respectively derived from delta and omicron VOCs, were constructed. The 2dRBD‐Fc induced potent humoral and cellular immune responses, while the immunogenicity of 2omRBD‐Fc was low. We also observed that sequential immunization with 2RBD‐Fc, 2dRBD‐Fc and 2omRBD‐Fc effectively elicited neutralizing antibodies against each immunized strain, and RBD‐specific T cell responses. To be noted, the Wuhan‐Hu‐1, delta and omicron neutralizing antibody titers induced by sequential immunization were comparable to that induced by repetitive immunization with 2RBD‐Fc, 2dRBD‐Fc or 2omRBD‐Fc respectively. The results suggest that sequential immunization with DNA vaccines encoding potent antigens derived from different VOCs, may be a promising strategy to elicit immune responses against multiple variants.

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Section: F I G U R E 4 (See Caption On Next Page)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Zhang

Wang

Yang

et al. 2023

Journal of Medical Virology

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“…Other researchers have also employed the use of advanced formulations to develop DNA vaccines against SARS-CoV-2 VOCs. One such approach was the development of a more universal DNA vaccine against SARS-CoV-2 which harbored antigenic regions from multiple SARS-CoV-2 strains [ 41 ]. More specifically, the vaccine was constructed using nucleotides encoding the receptor-binding domain, membrane, and nucleoproteins from the SARS-CoV-2 prototype Wuhan strain, as well as from the Alpha and Beta variants.…”

Section: Dna Vaccinesmentioning

confidence: 99%

Development of Next Generation Vaccines against SARS-CoV-2 and Variants of Concern

Yahaya

Khalid

Lim

et al. 2023

Viruses

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SARS-CoV-2 has caused the COVID-19 pandemic, with over 673 million infections and 6.85 million deaths globally. Novel mRNA and viral-vectored vaccines were developed and licensed for global immunizations under emergency approval. They have demonstrated good safety and high protective efficacy against the SARS-CoV-2 Wuhan strain. However, the emergence of highly infectious and transmissible variants of concern (VOCs) such as Omicron was associated with considerable reductions in the protective efficacy of the current vaccines. The development of next-generation vaccines that could confer broad protection against both the SARS-CoV-2 Wuhan strain and VOCs is urgently needed. A bivalent mRNA vaccine encoding the Spike proteins of both the SARS-CoV-2 Wuhan strain and the Omicron variant has been constructed and approved by the US FDA. However, mRNA vaccines are associated with instability and require an extremely low temperature (−80 °C) for storage and transportation. They also require complex synthesis and multiple chromatographic purifications. Peptide-based next-generation vaccines could be developed by relying on in silico predictions to identify peptides specifying highly conserved B, CD4+ and CD8+ T cell epitopes to elicit broad and long-lasting immune protection. These epitopes were validated in animal models and in early phase clinical trials to demonstrate immunogenicity and safety. Next-generation peptide vaccine formulations could be developed to incorporate only naked peptides, but they are costly to synthesize and production would generate extensive chemical waste. Continual production of recombinant peptides specifying immunogenic B and T cell epitopes could be achieved in hosts such as E. coli or yeast. However, recombinant protein/peptide vaccines require purification before administration. The DNA vaccine might serve as the most effective next-generation vaccine for low-income countries, since it does not require an extremely low temperature for storage or need extensive chromatographic purification. The construction of recombinant plasmids carrying genes specifying highly conserved B and T cell epitopes meant that vaccine candidates representing highly conserved antigenic regions could be rapidly developed. Poor immunogenicity of DNA vaccines could be overcome by the incorporation of chemical or molecular adjuvants and the development of nanoparticles for effective delivery.

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“…Studies have shown that in populations immunized with inactivated virus and the seropositivity rate is low, enhanced vaccinations significantly improves immunogenicity [ 162 , 163 ]. Appelberg et al [ 164 ] designed a universal SARS-CoV-2 DNA vaccine containing receptor-binding domain loops from the huCoV-19/WH01, the Alpha, and the Beta variants, combined with the membrane and nucleoproteins. The vaccine induced spike antibodies cross-reactive that neutralized huCoV-19/WH01, Beta, Delta, and Omicron virus in vitro, and primed nucleoprotein-specific T cells.…”

Section: Introductionmentioning

confidence: 99%

“…The vaccine induced spike antibodies cross-reactive that neutralized huCoV-19/WH01, Beta, Delta, and Omicron virus in vitro, and primed nucleoprotein-specific T cells. Priming of cross-reactive nucleoprotein-specific T cells alone was 60% protective [ 164 ]. Similarly, other teams also designed and developed multiple recombinant vaccines based on nucleoproteins [ 165 – 168 ].The results showed that recombinant vaccines could significantly increase the levels of serum neutralizing antibody and total immunoglobulin [ 165 ], and induce strong specific lymphocyte proliferative response and T cell response [ 165 ].…”

Section: Introductionmentioning

confidence: 99%

The SARS-CoV-2 nucleocapsid protein: its role in the viral life cycle, structure and functions, and use as a potential target in the development of vaccines and diagnostics

Cheng

Zhou

et al. 2023

Virol J

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Coronavirus disease 2019 (COVID-19) continues to take a heavy toll on personal health, healthcare systems, and economies around the globe. Scientists are expending tremendous effort to develop diagnostic technologies for detecting positive infections within the shortest possible time, and vaccines and drugs specifically for the prevention and treatment of COVID-19 disease. At the same time, emerging novel variants have raised serious concerns about vaccine efficacy. The SARS-CoV-2 nucleocapsid (N) protein plays an important role in the coronavirus life cycle, and participates in various vital activities after virus invasion. It has attracted a large amount of attention for vaccine and drug development. Here, we summarize the latest research of the N protein, including its role in the SARS-CoV-2 life cycle, structure and function, and post-translational modifications in addition to its involvement in liquid–liquid phase separation (LLPS) and use as a basis for the development of vaccines and diagnostic techniques.

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A universal SARS‐CoV DNA vaccine inducing highly cross‐reactive neutralizing antibodies and T cells

Cited by 14 publications

References 42 publications

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

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

Development of Next Generation Vaccines against SARS-CoV-2 and Variants of Concern

The SARS-CoV-2 nucleocapsid protein: its role in the viral life cycle, structure and functions, and use as a potential target in the development of vaccines and diagnostics

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