Parenteral Vaccination Can Be an Effective Means of Inducing Protective Mucosal Responses

ABSTRACTThe current paradigm in vaccine development is that nonreplicating vaccines delivered parenterally fail to induce immune responses in mucosal tissues. However, both clinical and experimental data have challenged this concept, and numerous studies have shown that induction of mucosal immune responses after parenteral vaccination is not a rare occurrence and might, in fact, significantly contribute to the protection against mucosal infections afforded by parenteral vaccines. While the mechanisms underlying this phenomenon are not well understood, the realization that parenteral vaccination can be an effective means of inducing protective mucosal responses is paradigm-shifting and has potential to transform the way vaccines are designed and delivered.

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Systemic and Mucosal Immune Responses to Cryptosporidium—Vaccine Development

Current Tropical Medicine Reports ◽

10.1007/s40475-015-0054-y ◽

2015 ◽

Vol 2 (3) ◽

pp. 171-180 ◽

Cited By ~ 16

Author(s):

Jacob G. Ludington ◽

Honorine D. Ward

Keyword(s):

Immune Responses ◽

Vaccine Development ◽

Mucosal Immune Responses

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VACCINE DEVELOPMENT & MODERN APPROACHES FOR COVID 19

Journal of Biomedical and Pharmaceutical Research ◽

10.32553/jbpr.v10i3.867 ◽

2021 ◽

Vol 10 (3) ◽

Author(s):

Soumya Rakshit ◽

Sabuj Kumar Bhattacharya ◽

Souvik Mallik ◽

Partha Sarathi Mondal ◽

Shibam Acharya ◽

...

Keyword(s):

Immune Responses ◽

Oral Delivery ◽

Bile Salts ◽

Vaccine Development ◽

Proteolytic Enzymes ◽

Oral Vaccine ◽

Low Ph ◽

Low Permeability ◽

Oral Vaccines ◽

Mucosal Tissues

Most of the infectious diseases due to pathogens are caused by the mucosal tract penetration. Hence, vaccines delivered directly to the mucosal tissues can defend pathogenic infections and provide protection at the first site of infection. Thus, mucosal, specifically, oral delivery is becoming the most ideal mode of vaccination. However, oral vaccines have to overcome numerous barriers such as the extremely low pH of the stomach, the presence of proteolytic enzymes and bile salts as well as low permeability in the intestine. Several formulations based on nanoparticles like liposomes, solid solutions, emulsions, VLPs are currently being used to prepare stable oral vaccine formulations. In current days different companies are trying to develop oral vaccine for COVID 19 also. This review briefly discusses several vaccine development criteria their mechanisms and various aspects of oral nanoparticles-based vaccine design that should be considered for improved mucosal and systemic immune responses. Keywords: Vaccine development, nanoparticles, liposome, VLP, COVID 19, mucosal immunity.

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Role of antigen specific T and B cells in systemic and mucosal immune responses in ETEC and Shigella infections, and their potential to serve as correlates of protection in vaccine development

Vaccine ◽

10.1016/j.vaccine.2019.03.040 ◽

2019 ◽

Vol 37 (34) ◽

pp. 4787-4793 ◽

Cited By ~ 1

Author(s):

Sachin Mani ◽

Franklin R. Toapanta ◽

Monica A. McArthur ◽

Firdausi Qadri ◽

Ann-Mari Svennerholm ◽

...

Keyword(s):

B Cells ◽

Immune Responses ◽

Vaccine Development ◽

T And B Cells ◽

Correlates Of Protection ◽

Mucosal Immune Responses

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Enhanced Mucosal Immune Responses to HIV Virus-Like Particles Containing a Membrane-Anchored Adjuvant

mBio ◽

10.1128/mbio.00328-10 ◽

2011 ◽

Vol 2 (1) ◽

Cited By ~ 43

Author(s):

Elena V. Vassilieva ◽

Bao-Zhong Wang ◽

Andrei N. Vzorov ◽

Li Wang ◽

Ying-Chun Wang ◽

...

Keyword(s):

Immune Responses ◽

Mucosal Immunity ◽

Vaccine Development ◽

Transmitted Disease ◽

Hiv Vaccine ◽

Antibody Responses ◽

Significant Drop ◽

Virus Like Particles ◽

Hiv Virus ◽

Mucosal Immune Responses

ABSTRACTPreviously, a modified HIV Env protein with a heterologous membrane anchor was found to be incorporated into HIV virus-like particles (VLPs) at 10-fold-higher levels than those of unmodified Env. To further improve the immunogenicity of such VLPs, membrane-anchored forms of bacterial flagellin (FliC) or a flagellin with a truncated variable region (tFliC) were constructed to be incorporated into the VLPs as adjuvants. HIV-specific immune responses induced by the resulting VLPs were determined in a guinea pig model. The VLPs induce enhanced systemic antibody responses by either systemic or mucosal vaccination and enhanced mucosal immunity by a mucosal immunization route, as demonstrated by high levels of HIV-specific serum IgG and mucosal IgG and IgA. The quality of the antibody responses was also improved, as shown by enhanced neutralization capacity. VLPs incorporating FliC were more effective in inducing systemic responses, while VLPs containing tFliC were more effective in inducing mucosal IgA responses. The IgG titers in sera were found to last for at least 5 months without a significant drop. These results indicate that HIV VLPs incorporating high levels of Env and a molecular adjuvant have excellent potential for further development as a prophylactic HIV vaccine.IMPORTANCEA prophylactic vaccine is urgently needed to control the spread of HIV/AIDS. Antigens inducing strong systemic and mucosal immune responses are promising as vaccines for this mucosally transmitted disease. We found that novel HIV virus-like particles (VLPs) presenting a high level of Env in its native membrane-bound form and coincorporating an innate immune-signaling adjuvant in the same particles were effective in inducing enhanced systemic and mucosal immunity. As new HIV vaccine candidates, these VLPs bridge the gaps of the innate and adaptive, as well as systemic and mucosal, immune responses, providing a new approach for HIV vaccine development.

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Characterization of Mucosal Immune Responses to Enterotoxigenic Escherichia coli Vaccine Antigens in a Human Challenge Model: Response Profiles after Primary Infection and Homologous Rechallenge with Strain H10407

Clinical and Vaccine Immunology ◽

10.1128/cvi.00617-15 ◽

2015 ◽

Vol 23 (1) ◽

pp. 55-64 ◽

Cited By ~ 20

Author(s):

Subhra Chakraborty ◽

Clayton Harro ◽

Barbara DeNearing ◽

Malathi Ram ◽

Andrea Feller ◽

...

Keyword(s):

Escherichia Coli ◽

Immune Response ◽

Immune Responses ◽

Vaccine Development ◽

Lavage Fluid ◽

Antibody Responses ◽

Enterotoxigenic Escherichia Coli ◽

Effective Vaccine ◽

Content Type ◽

Mucosal Immune Responses

ABSTRACTEnterotoxigenicEscherichia coli(ETEC) bacteria are the most common bacterial cause of diarrhea in children in resource-poor settings as well as in travelers. Although there are several approaches to develop an effective vaccine for ETEC, no licensed vaccines are currently available. A significant challenge to successful vaccine development is our poor understanding of the immune responses that correlate best with protection against ETEC illness. In this study, ETEC-specific mucosal immune responses were characterized and compared in subjects challenged with ETEC strain H10407 and in subjects rechallenged with the homologous organism. IgA responses to lipopolysaccharide (LPS), heat-labile toxin B subunit (LTB), and colonization factor antigen I (CFA/I) in antibody in lymphocyte supernatant (ALS), feces, lavage fluid, and saliva samples were evaluated. In all assay comparisons, ALS was the most sensitive indicator of a local immune response, but serum IgA was also a useful indirect marker of immune response to oral antigens. Volunteers challenged and then rechallenged with strain H10407 were protected from illness following rechallenge. Comparing mucosal antibody responses after primary and homologous rechallenge, protection against disease was reflected in reduced antibody responses to key ETEC antigens and in reduced fecal shedding of the H10407 challenge strain. Subjects challenged with strain H10407 mounted stronger antibody responses to LPS and LTB than subjects in the rechallenge group, while responses to CFA/I in the rechallenge group were higher than in the challenge group. We anticipate that this study will help provide an immunological benchmark for the evaluation of ETEC vaccines and immunization regimens in the future.

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Vaccines based on the cell surface carbohydrates of pathogenic bacteria

Anais da Academia Brasileira de Ciências ◽

10.1590/s0001-37652005000200009 ◽

2005 ◽

Vol 77 (2) ◽

pp. 293-324 ◽

Cited By ~ 115

Author(s):

Christopher Jones

Keyword(s):

Cell Surface ◽

Immune Responses ◽

Pathogenic Bacteria ◽

Vaccine Development ◽

Effective Means ◽

Haemophilus Influenzae Type ◽

Cell Surface Carbohydrate ◽

Wide Range ◽

Glycoconjugate Vaccines ◽

Surface Carbohydrates

Glycoconjugate vaccines, in which a cell surface carbohydrate from a micro-organism is covalently attached to an appropriate carrier protein are proving to be the most effective means to generate protective immune responses to prevent a wide range of diseases. The technology appears to be generic and applicable to a wide range of pathogens, as long as antibodies against surface carbohydrates help protect against infection. Three such vaccines, against Haemophilus influenzae type b, Neisseria meningitidis Group C and seven serotypes of Streptococcus pneumoniae, have already been licensed and many others are in development. This article discusses the rationale for the development and use of glycoconjugate vaccines, the mechanisms by which they elicit T cell-dependent immune responses and the implications of this for vaccine development, the role of physicochemical methods in the characterisation and quality control of these vaccines, and the novel products which are under development.

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A Bovine Enteric Mycobacterium Infection Model to Analyze Parenteral Vaccine-Induced Mucosal Immunity and Accelerate Vaccine Discovery

Frontiers in Immunology ◽

10.3389/fimmu.2020.586659 ◽

2020 ◽

Vol 11 ◽

Author(s):

Antonio Facciuolo ◽

Amy H. Lee ◽

Michael J. Trimble ◽

Neil Rawlyk ◽

Hugh G. G. Townsend ◽

...

Keyword(s):

Small Intestine ◽

Immune Responses ◽

Vaccine Development ◽

Natural Host ◽

Lymphoid Cells ◽

Intestinal Lumen ◽

Infection Model ◽

Enteric Infection ◽

Intestinal Segments ◽

Mucosal Immune Responses

Mycobacterial diseases of cattle are responsible for considerable production losses worldwide. In addition to their importance in animals, these infections offer a nuanced approach to understanding persistent mycobacterial infection in native host species. Mycobacteriumavium ssp. paratuberculosis (MAP) is an enteric pathogen that establishes a persistent, asymptomatic infection in the small intestine. Difficulty in reproducing infection in surrogate animal models and limited understanding of mucosal immune responses that control enteric infection in the natural host have been major barriers to MAP vaccine development. We previously developed a reproducible challenge model to establish a consistent MAP infection using surgically isolated intestinal segments prepared in neonatal calves. In the current study, we evaluated whether intestinal segments could be used to screen parenteral vaccines that alter mucosal immune responses to MAP infection. Using Silirum® – a commercial MAP bacterin – we demonstrate that intestinal segments provide a platform for assessing vaccine efficacy within a relatively rapid period of 28 days post-infection. Significant differences between vaccinates and non-vaccinates could be detected using quantitative metrics including bacterial burden in intestinal tissue, MAP shedding into the intestinal lumen, and vaccine-induced mucosal immune responses. Comparing vaccine-induced responses in mucosal leukocytes isolated from the site of enteric infection versus blood leukocytes revealed substantial inconsistences between these immune compartments. Moreover, parenteral vaccination with Silirum did not induce equal levels of protection throughout the small intestine. Significant control of MAP infection was observed in the continuous but not the discrete Peyer’s patches. Analysis of these regional mucosal immune responses revealed novel correlates of immune protection associated with reduced infection that included an increased frequency of CD335+ innate lymphoid cells, and increased expression of IL21 and IL27. Thus, intestinal segments provide a novel model to accelerate vaccine screening and discovery by testing vaccines directly in the natural host and provides a unique opportunity to interrogate mucosal immune responses to mycobacterial infections.

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