Alum/CpG Adjuvanted Inactivated COVID-19 Vaccine with Protective Efficacy against SARS-CoV-2 and Variants

Zhang, Yuntao; Zheng, Xiaotong; Wang, Sheng; Liang, Hongyang; Zhao, Yang; Zhu, Xiujuan; Yang, Rong; Zhang, Yadan; Dong, Xiaofei; Li, Weidong; Pei, Fei; Ding, Ling; Chang, Zhen; Deng, Li; Yuan, Gao; Yang, Zhaona; Zhu, Di; Yang, Xiaoming; Wang, Hui

doi:10.3390/vaccines10081208

Cited by 8 publications

(5 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CpG is an oligodeoxynucleotide that triggers Toll-like Receptor 9 (TLR9)-mediated innate immune responses that support subsequent adaptive immune responses 40 . Alum/CpG combination as an adjuvant was known to, directly and indirectly, activate many types of immune cells 41 .…”

Section: Discussionmentioning

confidence: 99%

Process development for an effective COVID-19 vaccine candidate harboring recombinant SARS-CoV-2 delta plus receptor binding domain produced by Pichia pastoris

Kalyoncu

Yılmaz

Kuyucu

et al. 2023

Sci Rep

View full text Add to dashboard Cite

Recombinant protein-based SARS-CoV-2 vaccines are needed to fill the vaccine equity gap. Because protein-subunit based vaccines are easier and cheaper to produce and do not require special storage/transportation conditions, they are suitable for low-/middle-income countries. Here, we report our vaccine development studies with the receptor binding domain of the SARS-CoV-2 Delta Plus strain (RBD-DP) which caused increased hospitalizations compared to other variants. First, we expressed RBD-DP in the Pichia pastoris yeast system and upscaled it to a 5-L fermenter for production. After three-step purification, we obtained RBD-DP with > 95% purity from a protein yield of > 1 g/L of supernatant. Several biophysical and biochemical characterizations were performed to confirm its identity, stability, and functionality. Then, it was formulated in different contents with Alum and CpG for mice immunization. After three doses of immunization, IgG titers from sera reached to > 106 and most importantly it showed high T-cell responses which are required for an effective vaccine to prevent severe COVID-19 disease. A live neutralization test was performed with both the Wuhan strain (B.1.1.7) and Delta strain (B.1.617.2) and it showed high neutralization antibody content for both strains. A challenge study with SARS-CoV-2 infected K18-hACE2 transgenic mice showed good immunoprotective activity with no viruses in the lungs and no lung inflammation for all immunized mice.

show abstract

Section: Discussionmentioning

confidence: 99%

Process development for an effective COVID-19 vaccine candidate harboring recombinant SARS-CoV-2 delta plus receptor binding domain produced by Pichia pastoris

Kalyoncu

Yılmaz

Kuyucu

et al. 2023

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Moreover, the vaccine exhibited equal effectiveness against the Beta, Delta, and Omicron variants through two immunization doses in rats, demonstrating its immune spectral properties. Positive correlations have been shown between virus-specific IgG antibody titers and COVID-19 severity [ 52 ].…”

Section: Oligonucleotide Adjuvantsmentioning

confidence: 99%

DNA Oligonucleotides as Antivirals and Vaccine Constituents against SARS Coronaviruses: A Prospective Tool for Immune System Tuning

Oberemok

Andreeva

Alieva

2023

IJMS

View full text Add to dashboard Cite

The SARS-CoV-2 pandemic has demonstrated the need to create highly effective antivirals and vaccines against various RNA viruses, including SARS coronaviruses. This paper provides a short review of innovative strategies in the development of antivirals and vaccines against SARS coronaviruses, with a focus on antisense antivirals, oligonucleotide adjuvants in vaccines, and oligonucleotide vaccines. Well-developed viral genomic databases create new opportunities for the development of innovative vaccines and antivirals using a post-genomic platform. The most effective vaccines against SARS coronaviruses are those able to form highly effective memory cells for both humoral and cellular immunity. The most effective antivirals need to efficiently stop viral replication without side effects. Oligonucleotide antivirals and vaccines can resist the rapidly changing genomic sequences of SARS coronaviruses using conserved regions of their genomes to generate a long-term immune response. Oligonucleotides have been used as excellent adjuvants for decades, and increasing data show that oligonucleotides could serve as antisense antivirals and antigens in vaccine formulations, becoming a prospective tool for immune system tuning.

show abstract

“…Recently, the combinatorial adjuvants have been well-studied in clinical practice. For example, aluminum hydroxide (AH) plus cytosine preceding guanosine (CpG) adjuvant triggered high levels of SARS-CoV-2-spike-specific IgG antibodies and neutralized antibodies against SARS-CoV-2 in rats [ 20 ], and combination adjuvant of aluminum hydroxide with poly (I : C) and CpG induced a stronger IgG1 and IgG2a immune response and boosted antigen uptake and activation of dendritic cells in vitro , by triggering an inflammatory response at the injection site similar to AH [ 21 ]. In addition, the formulation of cationic alpha-D-glucan nanoparticles and poly (I : C) adjuvant enhanced various cytokine mRNA expression in lymph nodes, induced high levels of virus-neutralizing antibodies in bronchoalveolar lavage fluid, and reduced microscopic lung lesions and virus load after swine influenza virus challenge [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

A Unique Combination of Mn2+ and Aluminum Adjuvant Acted the Synergistic Effect

Cen,

Chen,

Wei

et al. 2024

Canadian Journal of Infectious Diseases and Medical Microbiolog

View full text Add to dashboard Cite

Introduction. The development of combinatorial adjuvants is a promising strategy to boost vaccination efficiency. Accumulating evidence indicates that manganese exerts strong immunocompetence and will become an enormous potential adjuvant. Here, we described a novel combination of Mn2+ plus aluminum hydroxide (AH) adjuvant that significantly exhibited the synergistic immune effect. Methodology. Initially, IsdB3 proteins as the immune-dominant fragment of IsdB proteins derived from Staphylococcus aureus (S. aureus) were prepared. IsdB3 proteins were identified by western blotting. Furthermore, we immunized C57/B6 mice with IsdB3 proteins plus Mn2+ and AH adjuvant. After the second immunization, the proliferation of lymphocytes was measured by the cell counting kit-8 (CCK-8) and the level of IFN-γ, IL-4, IL-10, and IL-17 cytokine from spleen lymphocytes in mice and generation of the antibodies against IsdB3 in serum was detected with ELISA, and the protective immune response was assessed through S. aureus challenge. Results. IsdB3 proteins plus Mn2+ and AH obviously stimulated the proliferation of spleen lymphocytes and increased the secretion of IFN-γ, IL-4, IL-10, and IL-17 cytokine in mice, markedly enhanced the generation of the antibodies against IsdB3 in serum, observably decreased bacterial load in organs, and greatly improved the survival rate of mice. Conclusion. These data showed that the combination of Mn2+ and AH significantly acted a synergistic effect, reinforced the immunogenicity of IsdB3, and offered a new strategy to increase vaccine efficiency.

show abstract

Alum/CpG Adjuvanted Inactivated COVID-19 Vaccine with Protective Efficacy against SARS-CoV-2 and Variants

Cited by 8 publications

References 40 publications

Process development for an effective COVID-19 vaccine candidate harboring recombinant SARS-CoV-2 delta plus receptor binding domain produced by Pichia pastoris

Process development for an effective COVID-19 vaccine candidate harboring recombinant SARS-CoV-2 delta plus receptor binding domain produced by Pichia pastoris

DNA Oligonucleotides as Antivirals and Vaccine Constituents against SARS Coronaviruses: A Prospective Tool for Immune System Tuning

A Unique Combination of Mn2+ and Aluminum Adjuvant Acted the Synergistic Effect

Contact Info

Product

Resources

About