Baculoviral COVID-19 Delta DNA vaccine cross-protects against SARS-CoV2 variants in K18-ACE2 transgenic mice

Jang, Yuyeon; Cho, Hansam; Chun, Jungmin; Park, Kihoon; Nowakowska, Aleksandra; Kim, Jinha; Lee, Hyeondong; Lee, Chanyeong; Han, Yejo; Lee, Hee-Jung; Shin, Ha-Youn; Kim, Young Bong

doi:10.1016/j.vaccine.2022.12.067

Cited by 7 publications

(9 citation statements)

References 16 publications

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“…Jang et al (2022) reported the development of AcHERV-COVID19S, a human endogenous retrovirus (HERV)-enveloped recombinant baculoviral DNA vaccine against SARS-CoV-2 [ 42 ]. The researchers utilized a non-replicating recombinant baculovirus that delivered the SARS-CoV-2 S gene from the Wuhan strain.…”

Section: Dna Vaccinesmentioning

confidence: 99%

“…The vaccine also contained proline substitutions and the deletion of the polybasic cleavage site to enhance immunogenicity. The cross-protection offered by the AcHERV-COVID19S DNA vaccine against infections from SARS-CoV-2 Wuhan strain and VOCs such as the Delta and Omicron strain showed that mice immunized with the AcHERV-COVID19D DNA vaccine demonstrated 100% survival when challenged with Delta and Omicron VOCs and 71.4% survival against the prototype the SARS-CoV-2 Wuhan strain [ 42 ]. The elicitation of cellular immunity was also studied by the researchers who used ELISPOT analysis to show higher levels of IFN-γ-secreting splenocytes from the spleens of C57BL/6 mice immunized with the AcHERV-COVID19S DNA vaccine as compared to naïve mice.…”

Section: Dna Vaccinesmentioning

confidence: 99%

“…mRNA expression levels of TNF-α, IL-2, and IL-4 were shown to be much higher in mice which had received the vaccine when compared with the control group. Immunized mice showed more potent Th1 cell immune responses and maintained a greater level of Th1 cytokine mRNA than the placebo group [ 42 ]. This data provided evidence that the goal of development of vaccines that offered cross-protection against the spread of SARS-CoV-2 VOCs could be achieved.…”

Section: Dna Vaccinesmentioning

confidence: 99%

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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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Section: Dna Vaccinesmentioning

confidence: 99%

Section: Dna Vaccinesmentioning

confidence: 99%

Section: Dna Vaccinesmentioning

confidence: 99%

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

Yahaya

Khalid

Lim

et al. 2023

Viruses

View full text Add to dashboard Cite

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“…The recombinant baculovirus-based DNA vector system (AcHERV) is a viral gene delivery system for a vaccine platform and demonstrates effective immune responses, not only humoral immunity but also cellular immunity against viruses such as severe acute respiratory syndrome coronavirus-2 and Middle East respiratory syndrome coronavirus in previous studies, with their efficacy assessed and validated as high-performance vaccines [ 14 , 15 ]. Because of numerous CpG motifs in their genome, this baculovirus-based vaccine system serves as an effective adjuvant that induces efficient immune responses without the need for additional additives [ 16 , 17 , 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

Baculovirus Vector-Based Varicella-Zoster Virus Vaccine as a Promising Alternative with Enhanced Safety and Therapeutic Functions

Lee,

Kim,

Chun

et al. 2024

Vaccines

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Varicella-zoster virus (VZV) poses lifelong risks, causing varicella and herpes zoster (HZ, shingles). Currently, varicella and HZ vaccines are predominantly live attenuated vaccines or adjuvanted subunit vaccines utilizing VZV glycoprotein E (gE). Here, we propose our vaccine candidates involving a comparative analysis between recombinant baculoviral vector vaccines (AcHERV) and a live attenuated vaccine strain, vOka. AcHERV vaccine candidates were categorized into groups encoding gE only, VZV glycoprotein B (gB) only, or both gE and gB (gE-gB) as AcHERV-gE, AcHERV-gB, and AcHERV-gE-gB, respectively. Humoral immune responses were evaluated by analyzing total IgG, IgG1, IgG2a, and neutralizing antibodies. Cell-mediated immunity (CMI) responses were evaluated by enzyme-linked immunospot (ELISPOT) assay and Th1/Th2/Th17 cytokine profiling. In the mouse model, AcHERV-gE-gB elicited similar or higher total IgG, IgG2a, and neutralizing antibody levels than vOka and showed robust VZV-specific CMI responses. From the perspective of antigens encoded in vaccines and their relationship with CMI response, both AcHERV-gB and AcHERV-gE-gB demonstrated results equal to or superior to AcHERV-gE, encoding only gE. Taken together, these results suggest that AcHERV-gE-gB can be a novel candidate for alleviating risks of live attenuated vaccine-induced latency and effectively preventing varicella during early stages of life while providing strong CMI for effective resistance against HZ and therapeutic potential in later stages of life.

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“…Although animal-derived viral vectors excel in efficiently entering human cells, they often encounter challenges related to antibody formation and toxicity [ 5 ]. To overcome the problems of viral vector vaccines, a DNA vaccine platform technology using baculoviral vector was developed previously [ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Comparative Biodistribution Study of Baculoviral and Adenoviral Vector Vaccines against SARS-CoV-2

Lee,

Chun,

Kim

et al. 2023

J. Microbiol. Biotechnol.

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Various types of vaccines have been developed against COVID-19, including vector vaccines. Among the COVID-19 vaccines, AstraZeneca’s chimpanzee adenoviral vaccine was the first to be commercialized. For viral vector vaccines, biodistribution studies are critical to vaccine safety, gene delivery, and efficacy. This study compared the biodistribution of the baculoviral vector vaccine (AcHERV-COVID19) and the adenoviral vector vaccine (Ad-COVID19). Both vaccines were administered intramuscularly to mice, and the distribution of the SARS-CoV-2 S gene in each tissue was evaluated for up to 30 days. After vaccination, serum and various tissue samples were collected from the mice at each time point, and IgG levels and DNA copy numbers were measured using an enzyme-linked immunosorbent assay and a quantitative real-time polymerase chain reaction. AcHERV-COVID19 and Ad-COVID19 distribution showed that the SARS-CoV-2 spike gene remained predominantly at the injection site in the mouse muscle. In kidney, liver, and spleen tissues, the AcHERV-COVID19 group showed about 2–4 times higher persistence of the SARS-CoV-2 spike gene than the Ad-COVID19 group. The distribution patterns of AcHERV-COVID19 and Ad-COVID19 within various organs highlight their contrasting biodistribution profiles, with AcHERV-COVID19 exhibiting a broader and prolonged presence in the body compared to Ad-COVID19. Understanding the biodistribution profile of AcHERV-COVID19 and Ad-COVID19 could help select viral vectors for future vaccine development.

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Baculoviral COVID-19 Delta DNA vaccine cross-protects against SARS-CoV2 variants in K18-ACE2 transgenic mice

Cited by 7 publications

References 16 publications

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

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

Baculovirus Vector-Based Varicella-Zoster Virus Vaccine as a Promising Alternative with Enhanced Safety and Therapeutic Functions

Comparative Biodistribution Study of Baculoviral and Adenoviral Vector Vaccines against SARS-CoV-2

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