Insect cell-expressed hemagglutinin with CpG oligodeoxynucleotides plus alum as an adjuvant is a potential pandemic influenza vaccine candidate

Gong, Minqing; Zhou, Jun; Yang, Chi; Deng, Yao; Zhao, Guangyu; Zhang, Yonghui; Wang, Yue; Zhou, Yusen; Tan, Wenjie; Xu, Hui

doi:10.1016/j.vaccine.2012.10.054

Cited by 15 publications

(11 citation statements)

References 22 publications

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“…The results of the present study also support the importance of the Adjuvant System approach, although adjuvant combinations do not always produce the desired response, as seen with RBD/I+C. Consistent with the results of the present study, CpG plus alum was found to induce protective humoral, as well as cellular immunity, in mice immunised with a recombinant haemagglutinin vaccine that protected against influenza virus challenge [32] . The ideal immunity of the CpG and alum combination may be the result of mutual complementation of these two adjuvants.…”

Section: Discussionsupporting

confidence: 90%

Tailoring Subunit Vaccine Immunity with Adjuvant Combinations and Delivery Routes Using the Middle East Respiratory Coronavirus (MERS-CoV) Receptor-Binding Domain as an Antigen

et al. 2014

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The development of an effective vaccine is critical for prevention of a Middle East respiratory syndrome coronavirus (MERS-CoV) pandemic. Some studies have indicated the receptor-binding domain (RBD) protein of MERS-CoV spike (S) is a good candidate antigen for a MERS-CoV subunit vaccine. However, highly purified proteins are typically not inherently immunogenic. We hypothesised that humoral and cell-mediated immunity would be improved with a modification of the vaccination regimen. Therefore, the immunogenicity of a novel MERS-CoV RBD-based subunit vaccine was tested in mice using different adjuvant formulations and delivery routes. Different vaccination regimens were compared in BALB/c mice immunized 3 times intramuscularly (i.m.) with a vaccine containing 10 µg of recombinant MERS-CoV RBD in combination with either aluminium hydroxide (alum) alone, alum and polyriboinosinic acid (poly I:C) or alum and cysteine-phosphate-guanine (CpG) oligodeoxynucleotides (ODN). The immune responses of mice vaccinated with RBD, incomplete Freund’s adjuvant (IFA) and CpG ODN by a subcutaneous (s.c.) route were also investigated. We evaluated the induction of RBD-specific humoral immunity (total IgG and neutralizing antibodies) and cellular immunity (ELISpot assay for IFN-γ spot-forming cells and splenocyte cytokine production). Our findings indicated that the combination of alum and CpG ODN optimized the development of RBD-specific humoral and cellular immunity following subunit vaccination. Interestingly, robust RBD-specific antibody and T-cell responses were induced in mice immunized with the rRBD protein in combination with IFA and CpG ODN, but low level of neutralizing antibodies were elicited. Our data suggest that murine immunity following subunit vaccination can be tailored using adjuvant combinations and delivery routes. The vaccination regimen used in this study is promising and could improve the protection offered by the MERS-CoV subunit vaccine by eliciting effective humoral and cellular immune responses.

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Section: Discussionsupporting

confidence: 90%

Tailoring Subunit Vaccine Immunity with Adjuvant Combinations and Delivery Routes Using the Middle East Respiratory Coronavirus (MERS-CoV) Receptor-Binding Domain as an Antigen

et al. 2014

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“…Although the immune responses induced by polyanhydride nanovaccines against influenza are promising, recent literature suggests that novel combinations of adjuvants and/or delivery vehicles may enhance immune responses by targeting different immune pathways. − We previously demonstrated that hydrogels consisting of Pluronic F127 (PF127) and a pentablock copolymer based on PF127 with cationic polydiethylaminoethyl methacrylate (PDEAEM) outer blocks were effective gene, drug and protein delivery vectors. − The finding that hydrogels promoted the rapid development of high titer antibody responses against ovalbumin suggests this platform will be effective as a vaccine adjuvant and delivery vehicle for protein antigens. Because of the temperature-dependent gelation properties of PF127, these block copolymer hydrogels can be injected as liquid solutions and form gels at physiological temperature to create a depot at the injection site that typically lasts for 3–4 days followed by persistent low amounts of the hydrogel for up to one month postinjection .…”

Section: Introductionmentioning

confidence: 99%

Combination Nanovaccine Demonstrates Synergistic Enhancement in Efficacy against Influenza

Ross¹,

Adams²,

Loyd³

et al. 2016

ACS Biomater. Sci. Eng.

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H5N1 influenza virus has the potential to become a significant global health threat, and next generation vaccine technologies are needed. In this work, the combined efficacy of two nanoadjuvant platforms (polyanhydride nanoparticles and pentablock copolymer-based hydrogels) to induce protective immunity against H5N1 influenza virus was examined. Mice received two subcutaneous vaccinations (day 0 and 21) containing 10 μg of H5 hemagglutinin trimer alone or in combination with the nanovaccine platforms. Nanovaccine immunization induced high neutralizing antibody titers that were sustained through 70 days postimmunization. Finally, mice were intranasally challenged with A/H5N1 VNH5N1-PR8CDC-RG virus and monitored for 14 days. Animals receiving the combination nanovaccine had lower viral loads in the lung and weight loss after challenge in comparison to animals vaccinated with each platform alone. These data demonstrate the synergy between polyanhydride nanoparticles and pentablock copolymer-based hydrogels as adjuvants in the design of a more efficacious influenza vaccine.

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“…This indicated that alum and bacterial antigen (FKB) stimulated the immune responses to upregulate the expression of TLR9, which may facilitate the uptake of the CpG ODNs. CpG ODNs and alum worked synergistically to enhance immune-potentiating and antigen-sparing effects of a vaccine against swine influenza virus [63], which was not observed when CpG ODNs or alum was used alone. The increased expressions (~5 folds) of RCTLR9A and RCTLR9B in cobia injected with the control ODN 213 formulated with alum and FKB may be attributed to the immunostimulatory effects of alum and FKB.…”

Section: Discussionmentioning

confidence: 99%

The Effect of TLR9 Agonist CpG Oligodeoxynucleotides on the Intestinal Immune Response of Cobia (Rachycentron canadum)

Byadgi

Puteri

Lee

et al. 2014

Journal of Immunology Research

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Cytosine-guanine oligodeoxynucleotide (CpG ODN) motifs of bacterial DNA are recognized through toll-like receptor 9 (TLR9) and are potent activators of innate immunity. However, the interaction between TLR9 and CpG ODN in aquatic species has not been well characterized. Hence, cobia TLR9 isoform B (RCTLR9B) was cloned and its expression and induction in intestine were investigated. RCTLR9B cDNA consists of 3113bp encoding 1009 amino acids containing three regions, leucine rich repeats, transmembrane domain, and toll/interleukin-1 receptor (TIR) domain. Intraperitoneal injection of CpG ODN 2395 upregulated RCTLR9 A and B and MyD88 and also induced the expressions of Mx, chemokine CC, and interleukin IL-1β. Cobia intraperitoneally injected with CpG ODN 1668 and 2395 had increased survival rates after challenge with Photobacterium damselae subsp. piscicida. In addition, formulation of CpG ODN with formalin-killed bacteria (FKB) and aluminum hydroxide gel significantly increased expressions of RCTLR9 A (50 folds) and B (30 folds) isoforms at 10 dpi (CpG ODN 1668) and MyD88 (21 folds) at 6 dpv (CpG ODN 2395). Subsequently, IL-1β increased at 6 dpv in 1668 group. No histopathological damage and inflammatory responses were observed in the injected cobia. Altogether, these results facilitate CpG ODNs as an adjuvant to increase bacterial disease resistance and efficacy of vaccines in cobia.

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Insect cell-expressed hemagglutinin with CpG oligodeoxynucleotides plus alum as an adjuvant is a potential pandemic influenza vaccine candidate

Cited by 15 publications

References 22 publications

Tailoring Subunit Vaccine Immunity with Adjuvant Combinations and Delivery Routes Using the Middle East Respiratory Coronavirus (MERS-CoV) Receptor-Binding Domain as an Antigen

Tailoring Subunit Vaccine Immunity with Adjuvant Combinations and Delivery Routes Using the Middle East Respiratory Coronavirus (MERS-CoV) Receptor-Binding Domain as an Antigen

Combination Nanovaccine Demonstrates Synergistic Enhancement in Efficacy against Influenza

The Effect of TLR9 Agonist CpG Oligodeoxynucleotides on the Intestinal Immune Response of Cobia (Rachycentron canadum)

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