Evaluation of hyaluronic acid-based combination adjuvant containing monophosphoryl lipid A and aluminum salt for hepatitis B vaccine

Moon, S K; Shin, Eui‐Cheol; Noh, Young-Woock; Lim, Yong Taik

doi:10.1016/j.vaccine.2015.08.006

Cited by 26 publications

(24 citation statements)

References 40 publications

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“…Adjuvant System 04 (AS04), combining monophosphoryl lipid A (MPL) and aluminum salt, has been licensed for use in human vaccines (e.g., human papillomavirus and hepatitis B virus vaccines) with increased antibody titers (43, 44). Compared with aluminum adjuvant (hydroxide or salt) alone, the combination of MPL and aluminum salt may induce isotype-switched IgG antibody responses and significantly elevate total IgG and neutralizing antibodies as induced by subunit vaccines with an acceptable safety profile (45–47). Indeed, in this study, we found that the aluminum hydroxide and MPL adjuvant combination elicited high-titer neutralizing antibodies in conjugation with both the wild-type and mutant ZIKV EDIII vaccines.…”

Section: Discussionmentioning

confidence: 99%

Rational Design of Zika Virus Subunit Vaccine with Enhanced Efficacy

Tai

Chen

Zhao

et al. 2019

J Virol

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Zika virus (ZIKV) infection in pregnant women can lead to fetal deaths and malformations. We have previously reported that ZIKV envelope protein domain III (EDIII) is a subunit vaccine candidate with cross-neutralization activity; however, like many other subunit vaccines, its efficacy is limited. To improve the efficacy of this subunit vaccine, we identified a nonneutralizing epitope on ZIKV EDIII surrounding residue 375, which is buried in the full-length envelope protein but becomes exposed in recombinant EDIII. We then shielded this epitope with an engineered glycan probe. Compared to the wild-type EDIII, the mutant EDIII induced significantly stronger neutralizing antibodies in three mouse strains and also demonstrated significantly improved efficacy by fully protecting mice, particularly pregnant mice and their fetuses, against high-dose lethal ZIKV challenge. Moreover, the mutant EDIII immune sera significantly enhanced the passive protective efficacy by fully protecting mice against lethal ZIKV challenge; this passive protection was positively associated with neutralizing antibody titers. We further showed that the enhanced efficacy of the mutant EDIII was due to the shielding of the immunodominant nonneutralizing epitope surrounding residue 375, which led to immune refocusing on the neutralizing epitopes. Taken together, the results of this study reveal that an intrinsic limitation of subunit vaccines is their artificially exposed immunodominant nonneutralizing epitopes, which can be overcome through glycan shielding. Additionally, the mutant ZIKV protein generated in this study is a promising subunit vaccine candidate with high efficacy in preventing ZIKV infections in mice. IMPORTANCE Viral subunit vaccines generally show low efficacy. In this study, we revealed an intrinsic limitation of subunit vaccine designs: artificially exposed surfaces of subunit vaccines contain epitopes unfavorable for vaccine efficacy. More specifically, we identified an epitope on Zika virus (ZIKV) envelope protein domain III (EDIII) that is buried in the full-length envelope protein but becomes exposed in recombinant EDIII. We further shielded this epitope with a glycan, and the resulting mutant EDIII vaccine demonstrated significantly enhanced efficacy over the wild-type EDIII vaccine in protecting animal models from ZIKV infections. Therefore, the intrinsic limitation of subunit vaccines can be overcome through shielding these artificially exposed unfavorable epitopes. The engineered EDIII vaccine generated in this study is a promising vaccine candidate that can be further developed to battle ZIKV infections.

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Section: Discussionmentioning

confidence: 99%

Rational Design of Zika Virus Subunit Vaccine with Enhanced Efficacy

Tai

Chen

Zhao

et al. 2019

J Virol

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“…Although the existing HBV vaccine provides many people with significant protection against infection [13], a more effective vaccine is required for poor-response groups [14, 15]. In a previous study, we found an HBsAg-binding protein that could promote the immune process both in vitro and in vivo.…”

Section: Discussionmentioning

confidence: 99%

A Pre-Clinical Safety Evaluation of SBP (HBsAg-Binding Protein) Adjuvant for Hepatitis B Vaccine

Wang

Liu

et al. 2017

PLoS ONE

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Although adjuvants are a common component of many vaccines, there are few adjuvants licensed for use in humans due to concerns about their toxic effects. There is a need to develop new and safe adjuvants, because some existing vaccines have low immunogenicity among certain patient groups. In this study, SBP, a hepatitis B surface antigen binding protein that was discovered through screening a human liver cDNA expression library, was introduced into hepatitis B vaccine. A good laboratory practice, non-clinical safety evaluation was performed to identify the side effects of both SBP and SBP-adjuvanted hepatitis B vaccine. The results indicate that SBP could enhance the HBsAg-specific immune response, thus increasing the protection provided by the hepatitis B vaccine. The safety data obtained here warrant further investigation of SBP as a vaccine adjuvant.

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“…The co-administration of alum and a TLR-7 adjuvant enhanced memory B cell response to lymphocytic choriomeningitis virus (LCMV) antigen [ 35 ]. Alum in combination with MPLA-HA-adjuvanted HBsAg increased both the magnitude and the persistence of HBsAg-specific immune responses against hepatitis B virus infection [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

The Potency of an Anti-MERS Coronavirus Subunit Vaccine Depends on a Unique Combinatorial Adjuvant Formulation

George

Tai

et al. 2020

Vaccines

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Vaccination is one of the most successful strategies to prevent human infectious diseases. Combinatorial adjuvants have gained increasing interest as they can stimulate multiple immune pathways and enhance the vaccine efficacy of subunit vaccines. We investigated the adjuvanticity of Aluminum (alum) in combination with rASP-1, a protein adjuvant, using the Middle East respiratory syndrome coronavirus MERS-CoV receptor-binding-domain (RBD) vaccine antigen. A highly enhanced anti-MERS-CoV neutralizing antibody response was induced when mice were immunized with rASP-1 and the alum-adjuvanted RBD vaccine in two separate injection sites as compared to mice immunized with RBD + rASP-1 + alum formulated into a single inoculum. The antibodies produced also significantly inhibited the binding of RBD to its cell-associated receptor. Moreover, immunization with rASP-1 co-administered with the alum-adjuvanted RBD vaccine in separate sites resulted in an enhanced frequency of TfH and GC B cells within the draining lymph nodes, both of which were positively associated with the titers of the neutralizing antibody response related to anti-MERS-CoV protective immunity. Our findings not only indicate that this unique combinatorial adjuvanted RBD vaccine regimen improved the immunogenicity of RBD, but also point to the importance of utilizing combinatorial adjuvants for the induction of synergistic protective immune responses.

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Evaluation of hyaluronic acid-based combination adjuvant containing monophosphoryl lipid A and aluminum salt for hepatitis B vaccine

Cited by 26 publications

References 40 publications

Rational Design of Zika Virus Subunit Vaccine with Enhanced Efficacy

Rational Design of Zika Virus Subunit Vaccine with Enhanced Efficacy

A Pre-Clinical Safety Evaluation of SBP (HBsAg-Binding Protein) Adjuvant for Hepatitis B Vaccine

The Potency of an Anti-MERS Coronavirus Subunit Vaccine Depends on a Unique Combinatorial Adjuvant Formulation

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