Rodents as pre-clinical models for predicting vaccine performance in humans

Riese, Peggy; Trittel, Stephanie; Schulze, Kai; Guzmán, Carlos A.

doi:10.1586/14760584.2015.1074043

Cited by 10 publications

(13 citation statements)

References 116 publications

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“…For prevention and control of infectious diseases, vaccines are usually considered the most cost-efficient tools to block the transmission of pathogens [ 32 ]. However, the search for candidate antigens is one of the most difficult steps in the process.…”

Section: Discussionmentioning

confidence: 99%

“…Alpha-actinin, both native and recombinant, can be recognized by sera from women who have been exposed to T. vaginalis . It has been proved to be the most common immunogen with high immunogenicity [ 9 , 24 , 33 ], an essential requirement as a vaccine candidate [ 32 ]. Additionally, there is a very low similarity in amino acid sequences of the epitopes between T. vaginalis α-actinin and the corresponding human actinin homolog [ 21 , 34 ].…”

Section: Discussionmentioning

confidence: 99%

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Recombinant α-actinin subunit antigens of Trichomonas vaginalis as potential vaccine candidates in protecting against trichomoniasis

Xie

Gao

et al. 2017

Parasites Vectors

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BackgroundHuman trichomoniasis caused by Trichomonas vaginalis is one of the most common sexually transmitted diseases with more than 200 million cases worldwide. It has caused a series of health problems to patients. For prevention and control of infectious diseases, vaccines are usually considered as one of the most cost-efficient tools. However, until now, work on the development of T. vaginalis vaccines is still mainly focused on the screening of potential immunogens. Alpha-actinin characterized by high immunogenicity in T. vaginalis was suggested as a promising candidate. Therefore, the purpose of this study was to evaluate the protective potency of recombinant α-actinin against T. vaginalis infection in a mouse intraperitoneal model.MethodsTwo selected coding regions of α-actinin (ACT-F, 14–469 aa and ACT-T, 462–844 aa) amplified from cDNA were cloned into pET-32a (+) expression vector and transfected into BL21 cells. After induction with IPTG and purification with electroelution, the two recombinant fusion proteins were emulsified in Freund’s adjuvant (FA) and used to immunize BALB/C mice. Following intraperitoneal inoculation with T. vaginalis, the survival rate of mice was monitored for the assessment of protective potency. After immunization, the antibody level in mouse serum was assessed by ELISA, splenocyte proliferation response was detected with CCK8 and cytokines in the supernatant of splenocytes were quantified with a cytometric bead-based assay.ResultsWe successfully obtained purified ACT-F (70.33 kDa) and ACT-T (61.7kDa). Both recombinant proteins could provide significant protection against T. vaginalis challenge, especially ACT-T (with 100% protection within one month). Meanwhile, high levels of specific total IgG and subtypes (IgG1 > IgG2a) were detected in sera from the immunized mice. Our results also revealed a statistically significant increase in splenocyte proliferation and related cytokine (IFN-γ, IL-6, IL-17A and IL-10) production after repeated stimulation with the corresponding antigens in vitro.ConclusionsImmunization with both ACT-F and ACT-T could confer partial to complete protection and trigger strong Th1/Th2 mixed humoral and cellular immune responses in the mouse host. This suggested that recombinant α-actinin subunit antigens may be promising vaccine candidates against trichomoniasis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Recombinant α-actinin subunit antigens of Trichomonas vaginalis as potential vaccine candidates in protecting against trichomoniasis

Xie

Gao

et al. 2017

Parasites Vectors

View full text Add to dashboard Cite

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“…In these mice, researchers were able to model immune complex aggregation and extended-dose related ADA formation which closely mirror the phenomena observed in humans [41]. Vaccines are often evaluated in transgenic mice with a humanized haplotype, which has proved to be an effective tool for predicting CD4+ T cell activation [42, 43]. Savvy strategies like these are gradually improving our preclinical in vivo investigations, howbeit animal modeling remains an unreliable predictor of clinically relevant immunogenicity.…”

Section: Immunogenic Risk Factors and The Need For Predictive Toolsmentioning

confidence: 99%

Unraveling the Effect of Immunogenicity on the PK/PD, Efficacy, and Safety of Therapeutic Proteins

Smith

Manoli

Jaw

et al. 2016

Journal of Immunology Research

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Biologics have emerged as a powerful and diverse class of molecular and cell-based therapies that are capable of replacing enzymes, editing genomes, targeting tumors, and more. As this complex array of tools arises a distinct set of challenges is rarely encountered in the development of small molecule therapies. Biotherapeutics tend to be big, bulky, polar molecules comprised of protein and/or nucleic acids. Compared to their small molecule counterparts, they are fragile, labile, and heterogeneous. Their biodistribution is often limited by hydrophobic barriers which often restrict their administration to either intravenous or subcutaneous entry routes. Additionally, their potential for immunogenicity has proven to be a challenge to developing safe and reliably efficacious drugs. Our discussion will emphasize immunogenicity in the context of therapeutic proteins, a well-known class of biologics. We set out to describe what is known and unknown about the mechanisms underlying the interplay between antigenicity and immune response and their effect on the safety, efficacy, pharmacokinetics, and pharmacodynamics of these therapeutic agents.

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“…Animal models to evaluate human vaccine candidates have been widely utilized in research and development efforts (Gerdts et al, 2007) and are required for regulatory agency approvals (Riese et al, 2015). Unfortunately, animal models used for pre-clinical vaccine efficacy studies have some significant limitations (Centlivre and Combadiere, 2015).…”

Section: Introductionmentioning

confidence: 99%

“…Unfortunately, animal models used for pre-clinical vaccine efficacy studies have some significant limitations (Centlivre and Combadiere, 2015). Rodent models are relatively inexpensive, and there are many reagents available to characterize their immune responses (Riese et al, 2015). The ability to characterize the magnitude of an immunoglobulin or cell mediated response following vaccination of rodents is routine (Schunk and Macallum, 2005).…”

Section: Introductionmentioning

confidence: 99%

Systemic cytokine and chemokine responses in immunized mice challenged with staphylococcal enterotoxin B

Reichenberg

Garg

Fernalld

et al. 2017

Toxicon

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The cytokine storm induced by staphylococcal enterotoxin B (SEB) describes the rapid and dramatic induction of mediators which are likely responsible for the toxin’s deleterious effects. However despite the use of numerous animal models for investigating SEB related illness in humans, mechanisms of toxicity and correlates of protection remain unclear. In the present study, we used an LPS-potentiated model of SEB lethality to investigate the toxin-induced cytokine and chemokine responses in untreated and immunized mice. Of 30 separate mediators analyzed, serum levels for 28 or 27 of these cytokines and chemokines were elevated following administration of dosages of 3 or 30 LD50 of native SEB, respectively. Mice immunized with a non-toxic SEB vaccine candidate expressed in either E. coli or transgenic soy expression systems were protected from lethality when challenged with potentiated SEB. The majority of SEB-induced cytokines and chemokines (21 of 28 or 23 of 27 following challenge with dosages of 3 or 30 LD50 of native SEB, respectively) were significantly decreased in mice immunized with an SEB vaccine candidate when compared to control animals. Together, these studies provide the most comprehensive evaluation of the cytokine storm induced in this LPS-potentiated model of SEB lethality to date. As with other animal models, the identification of those mediators which are necessary and sufficient for SEB-induced toxicity remains unclear.

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Rodents as pre-clinical models for predicting vaccine performance in humans

Cited by 10 publications

References 116 publications

Recombinant α-actinin subunit antigens of Trichomonas vaginalis as potential vaccine candidates in protecting against trichomoniasis

Recombinant α-actinin subunit antigens of Trichomonas vaginalis as potential vaccine candidates in protecting against trichomoniasis

Unraveling the Effect of Immunogenicity on the PK/PD, Efficacy, and Safety of Therapeutic Proteins

Systemic cytokine and chemokine responses in immunized mice challenged with staphylococcal enterotoxin B

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