Comparison of four adjuvants revealed the strongest protection against lethal pneumococcal challenge following immunization with PsaA-PspA fusion protein and AS02 as adjuvant

Chen, Hong; Li, Bo; Yu, Jinfei; Zhang, Yue; Mo, Zujian; Gu, Tiejun; Kong, Wei; Zhang, Yong; Wu, Yongge

doi:10.1007/s00430-019-00579-9

Cited by 13 publications

(9 citation statements)

References 46 publications

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“…MF59, AS03, and AS02 are squalene-based oil-in-water emulsions with 150–160 nm particles. Squalene-based adjuvants were prepared as previously described, and all polydispersity indexes of these adjuvants are less than 0.15 ( 38 , 39 ). To ensure consistent adjuvant dose, each mouse was given an adjuvant totally containing 2.15 mg squalene at immunization.…”

Section: Methodsmentioning

confidence: 99%

Respiratory Syncytial Virus F Subunit Vaccine With AS02 Adjuvant Elicits Balanced, Robust Humoral and Cellular Immunity in BALB/c Mice

et al. 2020

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Respiratory syncytial virus (RSV) is a leading cause of lower respiratory illness, particularly in infants, the elderly, and immunocompromised adults. There is no licensed commercial vaccine against RSV. Importantly, formalin-inactivated RSV vaccines mediate enhanced respiratory disease. RSV fusion (F) protein with pre-fusion conformation is a promising candidate subunit vaccine. However, some problems remain to be solved, such as low immunogenicity and humoral immunity bias. Adjuvants can effectively enhance and adjust vaccine immune responses. In this study, we formulated pre-fusion RSV-F protein with the adjuvants, Alhydrogel, MF59, AS03, AS02, and glycol chitosan (GCS). We then conducted head-to-head comparisons of vaccine-induced immune responses in BALB/c mice. All adjuvanted vaccines enhanced antigen-specific and neutralizing antibody titers and viral clearance and gave an order of adjuvant activity: AS02 > AS03, MF59 > GCS, and Alhydrogel. Among them, AS02 elicited the highest antibody expression, which persisted until week 18. Moreover, AS02 significantly enhanced Th1 type immune response in immunized mice. Mice in the AS02 group also showed faster recovery from viral attacks in challenge tests. Further transcriptome analysis revealed that AS02 regulates immune balance by activating TLR-4 and promotes Th1-type immune responses. These results suggest that AS02 may be an excellent candidate adjuvant for RSV-F subunit vaccines. This study also provides valuable information regarding the effect of other adjuvants on immune responses of RSV-F subunit vaccines.

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Section: Methodsmentioning

confidence: 99%

Respiratory Syncytial Virus F Subunit Vaccine With AS02 Adjuvant Elicits Balanced, Robust Humoral and Cellular Immunity in BALB/c Mice

et al. 2020

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“…Conversely, in non-human primate studies, a robust opsonophagocytic response was induced by AS03 along with a robust NK cell-activating response 50 . Furthermore, AS03 incorporation into malaria and HIV vaccines drove high antigen-specific antibody levels 51 , 52 . Finally, both in mice and in vitro AS03 has resulted in a transient increase CCL2, CCL3, IL-6, CSF3, and CXCL1 47 and AS03 has been shown to improve the activation of naïve B cells or pre-existing memory B cells 11 , 53 .…”

Section: Discussionmentioning

confidence: 99%

Robust induction of functional humoral response by a plant-derived Coronavirus-like particle vaccine candidate for COVID-19

et al. 2023

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Despite the success of existing COVID-19 vaccine platforms, the persistent limitations in global deployment of vaccines and waning immunity exhibited by many of the currently deployed vaccine platforms have led to perpetual outbreaks of SARS-CoV-2 variants of concern. Thus, there is an urgent need to develop new durable vaccine candidates, to expand the global vaccine pipeline, and provide safe and effective solutions for every country worldwide. Here we deeply profiled the functional humoral response induced by two doses of AS03-adjuvanted and non-adjuvanted plant-derived Coronavirus-like particle (CoVLP) vaccine candidate from the phase 1 clinical trial, at peak immunogenicity and six months post-vaccination. AS03-adjuvanted CoVLP induced robust and durable SARS-CoV-2 specific humoral immunity, marked by strong IgG1antibody responses, potent FcγR binding, and antibody effector function. Contrary to a decline in neutralizing antibody titers, the FcγR2A-receptor binding capacity and antibody-mediated effector functions, such as opsonophagocytosis, remained readily detectable for at least six months.

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“… 49 However, the maintenance time of antibodies in the host still needs further investigation, and the specific mechanism is also related to the vaccine form. 50 In addition, the clearance and protective effects of fusion proteins against S. pneumoniae infections are related to IgG subtypes and cytokine secretion. Studies have shown that immunization with PiuA-PlyD4 and aluminum adjuvant can induce high levels of IgG1, IgG2a, and IgG2b antibodies in the host, indicating that the fusion protein not only stimulates the host to produce a high level of humoral immune response but also stimulates the Th1 and Th2 immune responses at the same time.…”

Section: Discussionmentioning

confidence: 99%

Immunoinformatics Prediction and Protective Efficacy of Vaccine Candidate PiuA-PlyD4 Against Streptococcus Pneumoniae

Miao,

Cui,

et al. 2023

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Purpose This study was designed to evaluate the immune protective efficacy of the novel Streptococcus pneumoniae (S. pneumoniae) protein vaccine PiuA-PlyD4 through immunoinformatics prediction and in vitro and in vivo experiments. Methods In this study, we conducted immunoinformatics prediction and protection analysis on the fusion protein PiuA-PlyD4. The epitope composition of the vaccine was analyzed based on the prediction of B-cell and helper T-cell epitopes. Meanwhile, the molecular docking of PiuA and TLR2/4 was simulated. After immunizing C57BL/6 mice with the prepared vaccine, the biological safety, immunogenicity and conservation were evaluated. By constructing different infection models and from the aspects of adhesion inhibition and cytokines, the protective effect of the fusion protein vaccine PiuA-PlyD4 on S. pneumoniae infection was explored. Results PiuA-PlyD4 has abundant B-cell and helper T-cell epitopes and shows a high antigenicity score and structural stability. Molecular docking analysis suggested the potential interaction between PiuA and TLR2/4. The specific antibody titer of fusion protein antiserum was as high as (7.81±2.32) ×10 5 . The protective effect of the immunized mice on nasal and lung colonization was significantly better than that of the control group, and the survival rate against S. pneumoniae infection of serotype 3 reached 50%. Cytokine detection showed that the humoral immune response, Th1, Th2 and Th17 cellular immune pathways were all involved in the process. Conclusion The study indicates that PiuA-PlyD4, whether the results are predicted by immunoinformatics or experimentally validated in vivo and in vitro, has good immunogenicity and immunoreactivity and can provide effective protection against S. pneumoniae infection. Therefore, it can be considered a promising prophylactic vaccine candidate for S. pneumoniae .

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Comparison of four adjuvants revealed the strongest protection against lethal pneumococcal challenge following immunization with PsaA-PspA fusion protein and AS02 as adjuvant

Cited by 13 publications

References 46 publications

Respiratory Syncytial Virus F Subunit Vaccine With AS02 Adjuvant Elicits Balanced, Robust Humoral and Cellular Immunity in BALB/c Mice

Respiratory Syncytial Virus F Subunit Vaccine With AS02 Adjuvant Elicits Balanced, Robust Humoral and Cellular Immunity in BALB/c Mice

Robust induction of functional humoral response by a plant-derived Coronavirus-like particle vaccine candidate for COVID-19

Immunoinformatics Prediction and Protective Efficacy of Vaccine Candidate PiuA-PlyD4 Against Streptococcus Pneumoniae

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