Immunization with DNA, adenovirus or both in biodegradable alginate microspheres: effect of route of inoculation on immune response

Mittal, Suresh K.; Aggarwal, Neeraj; Sailaja, G. S.; Olphen, Alberto van; HogenEsch, Harm; North, Adam; Hays, John P.; Moffatt, Stanley

doi:10.1016/s0264-410x(00)00170-5

Cited by 69 publications

(36 citation statements)

References 44 publications

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“…Other groups have similarly observed mucosal immune responses after parenteral inoculation with nucleic acid or protein subunit vaccines (48,50). The precise mechanism(s) for mucosal immune induction after parenteral inoculation with a nondisseminating vaccine is not known.…”

Section: Fig 5 Serum Igg Boost Responses From Nv1mentioning

confidence: 99%

Systemic, Mucosal, and Heterotypic Immune Induction in Mice Inoculated with Venezuelan Equine Encephalitis Replicons Expressing Norwalk Virus-Like Particles

Harrington¹,

Yount

Johnston³

et al. 2002

J Virol

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Norwalk-like viruses (NLVs) are a diverse group of single-stranded, nonenveloped, positive-polarity RNA viruses and are the leading cause of epidemic acute gastroenteritis in the United States. In this study, the major capsid gene of Norwalk virus, the prototype NLV, has been cloned and expressed in mammalian cells using a Venezuelan equine encephalitis (VEE) replicon expression system. Upon infection of baby hamster kidney (BHK) cells with VEE replicon particles (VRPs), the Norwalk virus capsid proteins self-assemble to generate high titers of Norwalk virus-like particles (VLPs) that are morphologically and antigenically analogous to wild-type Norwalk virus. Mice inoculated subcutaneously with VRPs expressing the Norwalk virus capsid protein (VRP-NV1) developed systemic and mucosal immune responses to Norwalk VLPs, as well as heterotypic antibody responses to the major capsid protein from another genogroup I NLV strain (NCFL) isolated from a recent outbreak. A second Norwalk virus capsid clone (NV2) containing three amino acid codon mutations from the NV1 clone was also expressed using VEE replicons (VRP-NV2), but upon infection of BHK cells failed to confer VLP self-assembly. Mice inoculated with VRP-NV2 elicited reduced systemic and mucosal immune responses to Norwalk VLPs, demonstrating the importance and potential utility of endogenous VLP presentation for maximum immune induction. Inoculation with either VRP-NV1 or VRP-NV2 resulted in serum antibody responses far superior to the induction in mice dosed orally with VLPs that were prepared using the VEE-NV1 replicon construct, a regimen similar to current models for NLV vaccination. Expression of NLV VLPs in mammalian cells offers a powerful approach for the design of novel NLV vaccines, either alone or in combination with current vaccination models.Norwalk-like viruses (NLVs) are the most frequent cause of epidemic gastroenteritis in the United States, infecting an estimated 23 million people each year, and have accounted for as much as 96% of selected outbreaks of acute, nonbacterial gastroenteritis (20,40,47). Persons of all ages are affected, and it is unclear whether infection typically confers long-term immunity (38). NLV outbreaks commonly occur within families, nursing homes, day care centers, schools, hospitals, and in the military (1,20,40,42). Infection with NLVs usually results in an episode of acute, self-limited gastroenteritis, with symptoms rarely more serious than nausea, vomiting, diarrhea, and lowgrade fever (40), and most outbreaks are likely not reported (47). However, using refined molecular detection methodologies, recent studies have extended the public health significance of NLV infections and suggest that NLVs are a common cause of severe diarrhea in children (22,53). Although further studies are necessary, NLVs may cause as much as 20% of endemic diarrheal disease in family settings in developed countries (42).The mortality attributable to NLV infection remains unclear, but fatalities among infected elderly may not be uncommon. It ...

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Section: Fig 5 Serum Igg Boost Responses From Nv1mentioning

confidence: 99%

Systemic, Mucosal, and Heterotypic Immune Induction in Mice Inoculated with Venezuelan Equine Encephalitis Replicons Expressing Norwalk Virus-Like Particles

Harrington¹,

Yount

Johnston³

et al. 2002

J Virol

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“…Sodium alginate-based biodegradable microparticles have been shown to encapsulate purified protein, bacteria, DNA or viruses and can be delivered to the animals by various routes of inoculation [Aggarwal et al 1999;Bowerstock T.L. et al 1999;Hilbert et al 1999;Mittal et al 2000;Periwal et al 1997]. Since alginate microspheres are biodegradable and no harsh treatments or organic solvents are used in the process of their synthesis, the viability of Ad vectors in these microparticles is usually very high.…”

Section: Vector Microencapsulationmentioning

confidence: 99%

Current Strategies and Future Directions for Eluding Adenoviral Vector Immunity

Bangari

Mittal²

2006

CGT

142

105

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Adenoviral (Ad) vectors can efficiently transduce a broad range of cell types and have been used extensively in preclinical and clinical studies for gene delivery applications. The presence of preexisting Ad immunity in the majority of human population and a rapid development of immune response against the Ad vector backbone following the first inoculation with the vector have impeded clinical use of these vectors. In addition, a number of animal inoculation studies have demonstrated that high systemic doses of Ad vectors invariably lead to initiation of acute inflammatory responses. This is mainly due to activation of innate immunity by vector particles. In general, vector and innate immune responses drastically limit the vector transduction efficiency and the duration of transgene expression. In order to have a predictable response with Ad vectors for gene therapy applications, the above limitations must be overcome. Strategies that are being examined to circumvent these drawbacks of Ad vectors include immunosuppression, immunomodulation, serotype switching, use of targeted Ad vectors, microencapsulation of Ad vectors, use of helper-dependent (HD) Ad vectors, and development of nonhuman Ad vectors. Here we review the current understanding of immune responses to Ad vectors, and recent advances in the strategies for immune evasion to improve the vector transduction efficiency and the duration of transgene expression. Development of novel strategies for targeting specific cell types would further boost the utility of Ad vectors by enhancing the safety, efficacy and duration of transgene expression.

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“…without any obvious side-effects. 34 We are working on the hypothesis that alginate microparticles are taken up by the cells via endocytosis and virus release from microparticles is mainly due to acidic pH and/or enzymatic digestion.…”

Section: Circumvention Of Vector-specific Immune Responsementioning

confidence: 99%

“…34 One milliliter suspension of microspheres was expected to contain a maximum of 5 Â 10 9 p.f.u. of AdCA36LacZ.…”

Section: Microencapsulation Of Had5 Recombinantmentioning

confidence: 99%

“…[24][25][26][27][28] Purified protein, DNA, bacteria, or viruses can be encapsulated in sodium alginate-based biodegradable microparticles, and can be delivered by various routes. [29][30][31][32][33][34] Since the vector immunity is still considered a major hurdle in obtaining persistent transgene expression on repeated inoculations with HAd5 vectors, we attempted to extend the available options for combating the vectorspecific immune response to microencapsulation of HAd5 vectors. This paper demonstrates that encapsulation of an HAd5 recombinant into alginate microparticles could evade the vector-specific immune response.…”

Section: Introductionmentioning

confidence: 99%

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Encapsulation of recombinant adenovirus into alginate microspheres circumvents vector-specific immune response

et al. 2002

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Pre-existing immunity against adenoviruses may compromise the efficacy of adenoviral vectors for vaccination and gene therapy. The purpose of this study was to determine whether encapsulation of adenovirus recombinants into biodegradable alginate microparticles could circumvent the vector-specific immune response. Mice were immunized either intranasally (i.n.) or intraperitoneally (i.p.) with human adenovirus type 5 (HAd5), resulting in the development of virus-specific antibodies. Immunized and naïve mice were inoculated with AdCA36lacZ (an E1-deleted HAd5 recombinant containing the bacterial b-galactosidase (LacZ) gene), encapsulated (E) into alginate microparticles, or nonencapsulated (NE) ie, as a virus suspension. LacZ expression in animals immunized once (1 Â ) or twice (2 Â ) with HAd5 and subsequently inoculated with NE-AdCA36lacZ (NE-Z) was significantly (Po0.001) reduced compared to those levels observed in NE-Z inoculated naïve mice, suggesting that the immune response against the vector adversely affected transgene expression. In contrast, there was only slight reduction (P40.05) in LacZ expression in mice immunized 1 Â or 2 Â with HAd5 that were subsequently inoculated with E-AdCA36lacZ (E-Z) compared to those levels obtained in E-Z inoculated naïve animals. Similar results were obtained with i.n. or i.p. inoculated animals. These results indicate that microencapsulation of recombinant adenovirus effectively circumvented the vector-specific immune response.

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Immunization with DNA, adenovirus or both in biodegradable alginate microspheres: effect of route of inoculation on immune response

Cited by 69 publications

References 44 publications

Systemic, Mucosal, and Heterotypic Immune Induction in Mice Inoculated with Venezuelan Equine Encephalitis Replicons Expressing Norwalk Virus-Like Particles

Systemic, Mucosal, and Heterotypic Immune Induction in Mice Inoculated with Venezuelan Equine Encephalitis Replicons Expressing Norwalk Virus-Like Particles

Current Strategies and Future Directions for Eluding Adenoviral Vector Immunity

Encapsulation of recombinant adenovirus into alginate microspheres circumvents vector-specific immune response

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