scholarly journals Recombinant Norwalk Virus-Like Particles Administered Intranasally to Mice Induce Systemic and Mucosal (Fecal and Vaginal) Immune Responses

2001 ◽  
Vol 75 (20) ◽  
pp. 9713-9722 ◽  
Author(s):  
Roberto A. Guerrero ◽  
Judith M. Ball ◽  
Sharon S. Krater ◽  
Susan E. Pacheco ◽  
John D. Clements ◽  
...  
Keyword(s):  
Immune Responses ◽  
Oral Route ◽  
Soluble Proteins ◽  
Mucosal Vaccine ◽  
Enzyme Linked Immunosorbent Assay ◽  
Low Doses ◽  
Norwalk Virus ◽  
Mucosal Adjuvant ◽  
Virus Like Particles ◽  
Serum Igg

ABSTRACT Recombinant Norwalk virus-like particles (rNV VLPs) were administered to BALB/c mice by the intranasal (i.n.) route to evaluate the induction of mucosal antibody responses. The results were compared to systemic and mucosal responses observed in new and previous studies (J. M. Ball, M. E. Hardy, R. L. Atmar, M. E. Connor, and M. K. Estes, J. Virol. 72:1345–1353, 1998) after oral administration of rNV VLPs. Immunizations were given in the presence or absence of a mucosal adjuvant, mutant Escherichia coliheat-labile toxin LT(R192G). rNV-specific immunoglobulin G (IgG) and fecal IgA were evaluated by enzyme-linked immunosorbent assay. The i.n. delivery of rNV VLPs was more effective than the oral route at inducing serum IgG and fecal IgA responses to low doses of rNV particles. Vaginal responses of female mice given VLPs by the i.n. and oral routes were also examined. All mice that received two immunizations with low doses i.n. (10 or 25 μg) of rNV VLPs and the majority of mice that received two high doses orally (200 μg) in the absence of adjuvant had rNV-specific serum IgG, fecal, and vaginal responses. Additional experiments evaluated whether rNV VLPs can function as a mucosal adjuvant by evaluating the immune responses to two soluble proteins, keyhole limpet hemocyanin and chicken egg albumin. Under the conditions tested, rNV VLPs did not enhance the serum IgG or fecal IgA response to these soluble proteins when coadministered by the i.n. or oral route. Low doses of nonreplicating rNV VLPs are immunogenic when administered i.n. in the absence of adjuvant, and addition of adjuvant enhanced the magnitude and duration of these responses. Recombinant NV VLPs represent a candidate mucosal vaccine for NV infections in humans.

scholarly journals Oral Immunization with Recombinant Norwalk Virus-Like Particles Induces a Systemic and Mucosal Immune Response in Mice

1998 ◽  
Vol 72 (2) ◽  
pp. 1345-1353 ◽  
Author(s):  
Judith M. Ball ◽  
Michele E. Hardy ◽  
Robert L. Atmar ◽  
Margaret E. Conner ◽  
Mary K. Estes
Keyword(s):  
Oral Delivery ◽  
Oral Immunization ◽  
Mucosal Immune Response ◽  
Mucosal Vaccine ◽  
Mouse Strains ◽  
Norwalk Virus ◽  
Mucosal Adjuvant ◽  
Virus Like Particles ◽  
Specific Serum ◽  
Intestinal Iga

ABSTRACT Recombinant Norwalk virus-like particles (rNV VLPs) produced in insect cells were evaluated as an oral immunogen in CD1 and BALB/c mice by monitoring rNV-specific serum total and subclass immunoglobulin G (IgG) and intestinal IgA responses. Dose and kinetics of response were evaluated in the presence and absence of the mucosal adjuvant cholera toxin (CT). rNV-specific serum IgG and intestinal IgA were detected in the absence of CT, and the number of responders was not significantly different from that of mice administered VLPs with CT at most doses. The use of CT was associated with induction of higher levels of IgG in serum; this effect was greater at higher doses of VLPs. IgG in serum was detected in the majority of animals by 9 days postimmunization (dpi), and intestinal IgA responses were detected by 24 dpi. In the absence of CT, IgG2b was the dominant IgG subclass response in both mouse strains. Thus, nonreplicating rNV VLPs are immunogenic when administered orally in the absence of any delivery system or mucosal adjuvant. These studies demonstrate that rNV VLPs are an excellent model to study the oral delivery of antigen, and they are a potential mucosal vaccine for NV infections.

scholarly journals An Intranasally Delivered Toll-Like Receptor 7 Agonist Elicits Robust Systemic and Mucosal Responses to Norwalk Virus-Like Particles

2010 ◽  
Vol 17 (12) ◽  
pp. 1850-1858 ◽  
Author(s):  
Lissette S. Velasquez ◽  
Brooke E. Hjelm ◽  
Charles J. Arntzen ◽  
Melissa M. Herbst-Kralovetz
Keyword(s):  
Immune Responses ◽  
Immune Protection ◽  
Norwalk Virus ◽  
Toll Like Receptor ◽  
Adjuvant Activity ◽  
Mucosal Adjuvant ◽  
Virus Like Particles ◽  
Vaccine Trials ◽  
Specific Serum ◽  
Tlr7 Agonist

ABSTRACT Norwalk virus (NV) is an enteric pathogen from the genus Norovirus and a major cause of nonbacterial gastroenteritis in humans. NV virus-like particles (VLPs) are known to elicit systemic and mucosal immune responses when delivered nasally; however, the correlates of immune protection are unknown, and codelivery with a safe and immunogenic mucosal adjuvant may enhance protective anti-NV immune responses. Resiquimod (R848), an imidazoquinoline-based Toll-like receptor 7 and/or 8 (TLR7/8) agonist, is being evaluated as an adjuvant in FDA-approved clinical vaccine trials. As such, we evaluated the adjuvant activity of two imidazoquinoline-based TLR7 and TLR7/8 agonists when codelivered intranasally with plant-derived NV VLPs. We also compared the activity of these agonists to the gold standard mucosal adjuvant, cholera toxin (CT). Our results indicate that codelivery with the TLR7 agonist, gardiquimod (GARD), induces NV VLP-specific serum IgG and IgG isotype responses and mucosal IgA responses in the gastrointestinal, respiratory, and reproductive tracts that are superior to those induced by R848 and comparable to those induced by the mucosal adjuvant CT. This study supports the continued investigation of GARD as a mucosal adjuvant for NV VLPs and possible use for other VLP-based vaccines for which immune responses at distal mucosal sites (e.g., respiratory and reproductive tracts) are desired.

Mucosal and systemic immune responses of mice to tetanus toxoid coadministered nasally with AFCo1

2011 ◽  
Vol 57 (3) ◽  
pp. 256-261 ◽  
Author(s):  
Belkis Romeu ◽  
Elyzabeth González ◽  
Judith del Campo ◽  
Reynaldo Acevedo ◽  
Caridad Zayas ◽  
...  
Keyword(s):  
Immune Responses ◽  
Tetanus Toxoid ◽  
Mucosal Vaccine ◽  
Vaccine Adjuvants ◽  
Mucosal Adjuvant ◽  
Mucosal Vaccines ◽  
Nasal Immunization ◽  
Human Use ◽  
Vaginal Wash ◽  
Systemic Compartment

Mucosal immune responses are an early and important line of defense against pathogens. The current understanding of the mucosal immune system allows us to consider the use of nasal immunization for induction of antigen-specific immune responses at the mucosal surface and the systemic compartment. Mucosal adjuvants are key for developing novel mucosal vaccines and represent 1 approach to improving mucosal and systemic immunity. However, few mucosal vaccine adjuvants are currently approved for human use. Neisseria meningitidis B proteoliposome-derived cochleate (AFCo1 — Adjuvant Finlay Cochleate 1) has been demonstrated to be a potent mucosal adjuvant. The present work demonstrates that intranasal immunization of 3 doses of tetanus toxoid (TT) coadministered with AFCo1 in mice promotes high systemic and mucosal responses. The anti-TT IgG serum titers and the mucosal anti-TT IgA in saliva and vaginal wash were significantly higher than TT alone. The analysis of antibody subclasses showed that intranasal administration of AFCo1 + TT induced not only IgG1 but also IgG2a anti-TT antibodies at levels comparable to those obtained with TT vaccine (vax-TET). These data support the fact that AFCo1 is a potent mucosal adjuvant in nasal immunization to a coadministered protein antigen.

scholarly journals Enzymatically polymerised polyphenols prepared from various precursors potentiate antigen-specific immune responses in both mucosal and systemic compartments in mice

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0246422
Author(s):  
Rui Tada ◽  
Miki Ogasawara ◽  
Daisuke Yamanaka ◽  
Yasuhiro Sakurai ◽  
Yoichi Negishi ◽  
...  
Keyword(s):  
Infectious Diseases ◽  
Immune Responses ◽  
Caffeic Acid ◽  
Intranasal Administration ◽  
Lavage Fluid ◽  
Modern Medicine ◽  
Mucosal Vaccine ◽  
Mucosal Adjuvant ◽  
Mucosal Vaccination ◽  
Nasal Vaccine

Despite significant modern medicine progress, having an infectious disease is a major risk factor for humans. Mucosal vaccination is now widely considered as the most promising strategy to defeat infectious diseases; however, only live-attenuated and inactivated mucosal vaccines are used in the clinical field. To date, no subunit mucosal vaccine was approved mainly because of the lack of safe and effective methodologies to either activate or initiate host mucosal immune responses. We have recently elucidated that intranasal administration of enzymatically polymerised caffeic acid potentiates antigen-specific mucosal and systemic antibody responses in mice. However, our earlier study has not confirmed whether these effects are specific to the polymer synthesised from caffeic acid. Here, we show that enzymatically polymerised polyphenols (EPPs) from various phenolic compounds possess mucosal adjuvant activities when administered nasally with an antigen to mice. Potentiation of antigen-specific immune responses by all EPPs tested in this study showed no clear difference among the precursors used. We found that intranasal administration of ovalbumin as the antigen, in combination with all enzymatically polymerised polyphenols used in this study, induced ovalbumin-specific mucosal IgA in the nasal cavity, bronchoalveolar lavage fluid, vaginal fluids, and systemic IgG, especially IgG1, in sera. Our results demonstrate that the mucosal adjuvant activities of polyphenols are not limited to polymerised caffeic acid but are broadly observable across the studied polyphenols. These properties of polyphenols may be advantageous for the development of safe and effective nasal vaccine systems to prevent and/or treat various infectious diseases.

scholarly journals A Double Mutant Heat-Labile Toxin from Escherichia coli, LT(R192G/L211A), Is an Effective Mucosal Adjuvant for Vaccination against Helicobacter pylori Infection

2013 ◽  
Vol 81 (5) ◽  
pp. 1532-1540 ◽  
Author(s):  
Louise Sjökvist Ottsjö ◽  
Carl-Fredrik Flach ◽  
John Clements ◽  
Jan Holmgren ◽  
Sukanya Raghavan
Keyword(s):  
Escherichia Coli ◽  
Helicobacter Pylori ◽  
Immune Responses ◽  
Double Mutant ◽  
Bacterial Load ◽  
Mucosal Vaccine ◽  
Mucosal Adjuvant ◽  
Content Type ◽  
Heat Labile ◽  
H Pylori

ABSTRACTHelicobacter pyloriinfection in the stomach is a common cause of peptic ulcer disease and is a strong risk factor for the development of gastric adenocarcinoma, yet no effective vaccine againstH. pyloriinfection is available to date. In mice, mucosal vaccination withH. pyloriantigens when given together with cholera toxin (CT) adjuvant, but not without adjuvant, can induce protective immune responses againstH. pyloriinfection. However, the toxicity of CT precludes its use as a mucosal adjuvant in humans. We evaluated a recently developed, essentially nontoxic double mutantEscherichia coliheat-labile toxin, LT(R192G/L211A) (dmLT), as a mucosal adjuvant in an experimentalH. pylorivaccine and compared it to CT in promoting immune responses and protection againstH. pyloriinfection in mice. Immunization via the sublingual or intragastric route withH. pylorilysate antigens and dmLT resulted in a significant decrease in bacterial load after challenge compared to that in unimmunized infection controls and to the same extent as when using CT as an adjuvant. Cellular immune responses in the sublingually immunized mice known to correlate with protection were also fully comparable when using dmLT and CT as adjuvants, resulting in enhancedin vitroproliferative and cytokine responses from spleen and mesenteric lymph node cells toH. pyloriantigens. Our results suggest that dmLT is an attractive adjuvant for inclusion in a mucosal vaccine againstH. pyloriinfection.

Humoral, mucosal, and cellular immune responses to oral Norwalk virus-like particles in volunteers

2003 ◽  
Vol 108 (3) ◽  
pp. 241-247 ◽  
Author(s):  
Carol O Tacket ◽  
Marcelo B Sztein ◽  
Genevieve A Losonsky ◽  
Steven S Wasserman ◽  
Mary K Estes
Keyword(s):  
Immune Responses ◽  
Norwalk Virus ◽  
Virus Like Particles ◽  
Cellular Immune Responses ◽  
Cellular Immune

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

2002 ◽  
Vol 76 (2) ◽  
pp. 730-742 ◽  
Author(s):  
Patrick R. Harrington ◽  
Boyd Yount ◽  
Robert E. Johnston ◽  
Nancy Davis ◽  
Christine Moe ◽  
...  
Keyword(s):  
Immune Responses ◽  
Capsid Protein ◽  
Mammalian Cells ◽  
Antibody Responses ◽  
Norwalk Virus ◽  
Venezuelan Equine Encephalitis ◽  
Virus Capsid ◽  
Virus Like Particles ◽  
Bhk Cells ◽  
Mucosal Immune Responses

ABSTRACT 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.

scholarly journals Assembly and Biological and Immunological Properties of Newcastle Disease Virus-Like Particles

2010 ◽  
Vol 84 (9) ◽  
pp. 4513-4523 ◽  
Author(s):  
Lori W. McGinnes ◽  
Homer Pantua ◽  
Jason P. Laliberte ◽  
Kathryn A. Gravel ◽  
Surbhi Jain ◽  
...  
Keyword(s):  
Immune Responses ◽  
Newcastle Disease Virus ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Intracellular Cytokine Staining ◽  
Nipah Virus ◽  
Vaccine Virus ◽  
Enzyme Linked Immunosorbent Assay ◽  
Virus Like Particles ◽  
Red Blood Cell Membranes

ABSTRACT Virus-like particles (VLPs) released from avian cells expressing the Newcastle disease virus (NDV) strain AV proteins NP, M, HN (hemagglutinin-neuraminidase), and F were characterized. The VLP-associated HN and F glycoproteins directed the attachment of VLPs to cell surfaces and fusion of VLP membranes with red blood cell membranes, indicating that they were assembled into VLPs in an authentic conformation. These particles were quantitatively prepared and used as an immunogen, without adjuvant, in BALB/c mice. The resulting immune responses, detected by enzyme-linked immunosorbent assay (ELISA), virus neutralization, and intracellular cytokine staining, were comparable to the responses to equivalent amounts of inactivated NDV vaccine virus. HN and F proteins from another strain of NDV, strain B1, could be incorporated into these VLPs. Foreign peptides were incorporated into these VLPs when fused to the NP or HN protein. The ectodomain of a foreign glycoprotein, the Nipah virus G protein, fused to the NDV HN protein cytoplasmic and transmembrane domains was incorporated into ND VLPs. Thus, ND VLPs are a potential NDV vaccine candidate. They may also serve as a platform to construct vaccines for other pathogens.

scholarly journals Mucosal Adjuvant Properties of the Shigella Invasin Complex

2006 ◽  
Vol 74 (5) ◽  
pp. 2856-2866 ◽  
Author(s):  
Robert W. Kaminski ◽  
K. Ross Turbyfill ◽  
Edwin V. Oaks
Keyword(s):  
Immune Responses ◽  
Binding Capacity ◽  
Lymphoid Cells ◽  
Mucosal Vaccine ◽  
Vaccine Antigen ◽  
Interleukin 4 ◽  
Cell Binding ◽  
Th2 Response ◽  
Mucosal Adjuvant ◽  
Mucosal Antibody

ABSTRACT The Shigella invasin complex (Invaplex) is an effective mucosal vaccine capable of protecting against Shigella challenge in animal models. The major antigenic constituents of Invaplex are the Ipa proteins and lipopolysaccharide. The cell-binding capacity of the Ipa proteins prompted the investigation into the adjuvanticity of Invaplex. Using ovalbumin (OVA) as a model antigen, intranasal immunization with OVA combined with Invaplex was found to enhance anti-OVA serum immunoglobulin G (IgG) and IgA responses and induce OVA-specific mucosal antibody responses at sites located both proximal and distal to the immunization site. The immune responses induced with OVA and Invaplex were comparable in both magnitude and duration to the immune responses induced after immunization with OVA and cholera toxin. The OVA-specific immune response was characterized by high levels of serum IgG1 and increased production of interleukin-4 (IL-4), IL-5, or IL-10 from lymphoid cells of immunized animals, suggesting a Th2 response. In addition to enhancing the immunogenicity of OVA, Invaplex-specific immune responses were also induced, indicating the potential for the development of a combination vaccine consisting of Invaplex and other immunogens. Preexisting Invaplex-specific immunity did not interfere with the capacity to enhance the immunogenicity of a second, unrelated vaccine antigen, suggesting that Invaplex could be used as a mucosal adjuvant in multiple vaccine regimens.

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