Immunogenicity and protection in small-animal models with controlled-release tetanus toxoid microparticles as a single-dose vaccine

Singh, Manmohan; Li, X M; Wang, H; McGee, John P.; Zamb, Timothy J.; Koff, Wayne C.; Wang, C Y; O’Hagan, Derek T.

doi:10.1128/iai.65.5.1716-1721.1997

Cited by 75 publications

(19 citation statements)

References 31 publications

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“…In addition to the use of microparticles to deliver adjuvants, microparticles may also be used in conjunction with traditional adjuvants, including alum. 131,132 In addition, microparticles may also be combined with emulsion-based adjuvants to improve their potency. 133,134…”

Section: Combinations Of Delivery Systems and Adjuvantsmentioning

confidence: 99%

Mucosal adjuvants and delivery systems for protein‐, DNA‐ and RNA‐based vaccines

Vajdy¹,

Srivastava²,

Polo³

et al. 2004

Immunol Cell Biol

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Almost all vaccinations today are delivered through parenteral routes. Mucosal vaccination offers several benefits over parenteral routes of vaccination, including ease of administration, the possibility of self-administration, elimination of the chance of injection with infected needles, and induction of mucosal as well as systemic immunity. However, mucosal vaccines have to overcome several formidable barriers in the form of significant dilution and dispersion; competition with a myriad of various live replicating bacteria, viruses, inert food and dust particles; enzymatic degradation; and low pH before reaching the target immune cells. It has long been known that vaccination through mucosal membranes requires potent adjuvants to enhance immunogenicity, as well as delivery systems to decrease the rate of dilution and degradation and to target the vaccine to the site of immune function. This review is a summary of current approaches to mucosal vaccination, and it primarily focuses on adjuvants as immunopotentiators and vaccine delivery systems for mucosal vaccines based on protein, DNA or RNA. In this context, we define adjuvants as protein or oligonucleotides with immunopotentiating properties co-administered with pathogenderived antigens, and vaccine delivery systems as chemical formulations that are more inert and have less immunomodulatory effects than adjuvants, and that protect and deliver the vaccine through the site of administration. Although vaccines can be quite diverse in their composition, including inactivated virus, virus-like particles and inactivated bacteria (which are inert), protein-like vaccines, and non-replicating viral vectors such as poxvirus and adenovirus (which can serve as DNA delivery systems), this review will focus primarily on recombinant protein antigens, plasmid DNA, and alphavirus-based replicon RNA vaccines and delivery systems. This review is not an exhaustive list of all available protein, DNA and RNA vaccines, with related adjuvants and delivery systems, but rather is an attempt to highlight many of the currently available approaches in immunopotentiation of mucosal vaccines.Key words: adjuvant, delivery system, immunomodulator, mucosal, vaccine. Recombinant protein vaccinesTraditional vaccines have comprised live-attenuated microbes, inactivated microorganisms, purified microbial components, polysaccharide-carrier protein conjugates or recombinant proteins. The first of the latter type of vaccine was derived from the diphtheria and tetanus toxoids, and was developed in the first half of the twentieth century. The two toxins were chemically detoxified to produce the non-toxic toxoids. Conventional approaches to vaccine development have been based on biochemical, immunological and microbiological methods that have been labourious, time-consuming and have allowed identification of the most abundant antigens of any given pathogen. Recent progress in DNA sequencing and subsequently in bioinformatics have resulted in advances in vaccine development. When the whole sequence of ...

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Section: Combinations Of Delivery Systems and Adjuvantsmentioning

confidence: 99%

Mucosal adjuvants and delivery systems for protein‐, DNA‐ and RNA‐based vaccines

Vajdy¹,

Srivastava²,

Polo³

et al. 2004

Immunol Cell Biol

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“…6,10,11,15 In rats, 1 dose of tetanus toxoid with a microparticle adjuvant gave immunity comparable to 3 doses with alum. 36 Microparticles can induce CMI, including CTLs, as well as humoral immunity. 6 They usually are not immunomodulators, but immunomodulators can be incorporated to improve their effectiveness.…”

Section: Nanoparticles and Microparticlesmentioning

confidence: 99%

Adjuvants in Veterinary Vaccines: Modes of Action and Adverse Effects

Spickler

Roth

2003

Veterinary Internal Medicne

165

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Vaccine adjuvants are chemicals, microbial components, or mammalian proteins that enhance the immune response to vaccine antigens. Interest in reducing vaccine-related adverse effects and inducing specific types of immunity has led to the development of numerous new adjuvants. Adjuvants in development or in experimental and commercial vaccines include aluminum salts (alum), oil emulsions, saponins, immune-stimulating complexes (ISCOMs), liposomes, microparticles, nonionic block copolymers, derivatized polysaccharides, cytokines, and a wide variety of bacterial derivatives. The mechanisms of action of these diverse compounds vary, as does their induction of cell-mediated and antibody responses. Factors influencing the selection of an adjuvant include animal species, specific pathogen, vaccine antigen, route of immunization, and type of immunity needed.

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“…Significant improvement in antibody titres has been shown in previous studies, when some part of antigen dose is administered as alum adsorbed antigen, while rest of the dose is given in microencapsulated form. 30 Interestingly, similar observations were found in the present study as well.…”

Section: Discussionmentioning

confidence: 99%

“…28 Previous reports have suggested the positive role of alum on improved antibody response from immunization with mixture of alum and antigen-loaded microparticle. [30][31][32][33][34] The presence of alum probably helps in better presentation of the soluble antigen released from the particles. 35,36 It could be due to the reason that released antigen gets adsorbed on to the alum and is then presented to APCs.…”

Section: Discussionmentioning

confidence: 99%

Immunogenicity and contraceptive efficacy of recombinant fusion protein encompassing Sp17 spermatozoa‐specific protein and GnRH: Relevance of adjuvants and microparticles based delivery to minimize number of injections

Minhas

Kumar

Moitra

et al. 2020

American J Rep Immunol

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Problem Requirement of multiple injections of contraceptive vaccines to achieve infertility is one of the important impediments for their application. In the present study, attempts have been made to reduce the number of injections of contraceptive vaccine. Method of study Fusion protein encompassing C‐terminus fragment of sperm protein Sp17 (aa residues 76‐126) and two copies of gonadotropin‐releasing hormone along with T‐cell epitopes and dilysine linkers (abbreviated as Sp17C‐GnRH2) was expressed in Escherichia coli. Its immunogenicity and contraceptive efficacy have been evaluated in female FVB/J mice using different adjuvants and delivery platforms. Results Immunization of female mice with recombinant Sp17C‐GnRH2 (25 μg/injection/mouse) emulsified with squalene‐arlacel A following two injections schedule led to failure of 88.8% immunized animals to conceive, which was not significantly different from mice immunized with same protein along with alum following three injections schedule. To make single‐dose vaccine, poly d,l‐lactic acid–based microparticles (PLA‐MPs) entrapping Sp17C‐GnRH2 were prepared. Immunization of female mice with a combination of soluble Sp17C‐GnRH2 (12.5 μg/injection/mouse) along with Sp17C‐GnRH2 entrapped in PLA‐MPs (12.5 μg/injection/mouse) in alum showed higher antibody titres and contraceptive efficacy as compared to mice immunized with Sp17C‐GnRH2 entrapped in PLA‐MPs alone in alum. Immunization with recombinant Sp17C‐GnRH2 led to long‐term infertility as second mating (150 days after immunization) of various groups of immunized mice showed similar infertility as observed during first mating. Conclusion Single‐dose immunization with PLA‐MPs entrapping Sp17C‐GnRH2 along with soluble recombinant protein in alum generated long‐lasting infertility in female mice.

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Immunogenicity and protection in small-animal models with controlled-release tetanus toxoid microparticles as a single-dose vaccine

Cited by 75 publications

References 31 publications

Mucosal adjuvants and delivery systems for protein‐, DNA‐ and RNA‐based vaccines

Mucosal adjuvants and delivery systems for protein‐, DNA‐ and RNA‐based vaccines

Adjuvants in Veterinary Vaccines: Modes of Action and Adverse Effects

Immunogenicity and contraceptive efficacy of recombinant fusion protein encompassing Sp17 spermatozoa‐specific protein and GnRH: Relevance of adjuvants and microparticles based delivery to minimize number of injections

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