Oral Vaccine Development by Molecular Display Methods Using Microbial Cells

2016 ◽  
pp. 497-509 ◽  
Author(s):  
Seiji Shibasaki ◽  
Mitsuyoshi Ueda
Keyword(s):  
Vaccine Development ◽  
Oral Vaccine ◽  
Microbial Cells ◽  
Molecular Display

scholarly journals A Systems Biology Approach Identifies B Cell Maturation Antigen (BCMA) as a Biomarker Reflecting Oral Vaccine Induced IgA Antibody Responses in Humans

2021 ◽  
Vol 12 ◽  
Author(s):  
Lynda Mottram ◽  
Anna Lundgren ◽  
Ann-Mari Svennerholm ◽  
Susannah Leach
Keyword(s):  
Systems Biology ◽  
Immune Responses ◽  
B Cell ◽  
Vaccine Development ◽  
Oral Vaccine ◽  
Antibody Responses ◽  
Cell Maturation ◽  
Antigen Specificity ◽  
B Cell Maturation ◽  
B Cell Maturation Antigen

Vaccines against enteric diseases could improve global health. Despite this, only a few oral vaccines are currently available for human use. One way to facilitate such vaccine development could be to identify a practical and relatively low cost biomarker assay to assess oral vaccine induced primary and memory IgA immune responses in humans. Such an IgA biomarker assay could complement antigen-specific immune response measurements, enabling more oral vaccine candidates to be tested, whilst also reducing the work and costs associated with early oral vaccine development. With this in mind, we take a holistic systems biology approach to compare the transcriptional signatures of peripheral blood mononuclear cells isolated from volunteers, who following two oral priming doses with the oral cholera vaccine Dukoral®, had either strong or no vaccine specific IgA responses. Using this bioinformatical method, we identify TNFRSF17, a gene encoding the B cell maturation antigen (BCMA), as a candidate biomarker of oral vaccine induced IgA immune responses. We then assess the ability of BCMA to reflect oral vaccine induced primary and memory IgA responses using an ELISA BCMA assay on a larger number of samples collected in clinical trials with Dukoral® and the oral enterotoxigenic Escherichia coli vaccine candidate ETVAX. We find significant correlations between levels of BCMA and vaccine antigen-specific IgA in antibodies in lymphocyte secretion (ALS) specimens, as well as with proportions of circulating plasmablasts detected by flow cytometry. Importantly, our results suggest that levels of BCMA detected early after primary mucosal vaccination may be a biomarker for induction of long-lived vaccine specific memory B cell responses, which are otherwise difficult to measure in clinical vaccine trials. In addition, we find that ALS-BCMA responses in individuals vaccinated with ETVAX plus the adjuvant double mutant heat-labile toxin (dmLT) are significantly higher than in subjects given ETVAX only. We therefore propose that as ALS-BCMA responses may reflect the total vaccine induced IgA responses to oral vaccination, this BCMA ELISA assay could also be used to estimate the total adjuvant effect on vaccine induced-antibody responses, independently of antigen specificity, further supporting the usefulness of the assay.

scholarly journals Specific immunity Induction at the mucosal level by viablelactobacillus casei:a Perspective for oral vaccine development

1998 ◽  
Vol 10 (1) ◽  
pp. 79-87 ◽  
Author(s):  
Susana Alvarez ◽  
Nadia Gobbato ◽  
Elena Bru ◽  
Aida P. De Ruiz Holgado ◽  
Gabriela Perdigón
Keyword(s):  
Vaccine Development ◽  
Oral Vaccine ◽  
Specific Immunity

scholarly journals Nano and Microparticles as Potential Oral Vaccine Carriers and Adjuvants Against Infectious Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Seyed Davoud Jazayeri ◽  
Hui Xuan Lim ◽  
Kamyar Shameli ◽  
Swee Keong Yeap ◽  
Chit Laa Poh
Keyword(s):  
Infectious Diseases ◽  
Immune Responses ◽  
Vaccine Development ◽  
Proteolytic Enzymes ◽  
Oral Vaccine ◽  
Oral Immunization ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Mucosal Surfaces ◽  
Successful Vaccine

Mucosal surfaces are the first site of infection for most infectious diseases and oral vaccination can provide protection as the first line of defense. Unlike systemic administration, oral immunization can stimulate cellular and humoral immune responses at both systemic and mucosal levels to induce broad-spectrum and long-lasting immunity. Therefore, to design a successful vaccine, it is essential to stimulate the mucosal as well as systemic immune responses. Successful oral vaccines need to overcome the harsh gastrointestinal environment such as the extremely low pH, proteolytic enzymes, bile salts as well as low permeability and the low immunogenicity of vaccines. In recent years, several delivery systems and adjuvants have been developed for improving oral vaccine delivery and immunogenicity. Formulation of vaccines with nanoparticles and microparticles have been shown to improve antigen stability, availability and adjuvanticity as well as immunostimulatory capacity, target delivery and specific release. This review discusses how nanoparticles (NPs) and microparticles (MPs) as oral carriers with adjuvant characteristics can be beneficial in oral vaccine development.

scholarly journals Home Administration of CVD 103-HgR: A Live Attenuated Oral Cholera Vaccine

2021 ◽  
Vol 104 (4) ◽  
pp. 1232-1240
Author(s):  
R. Paul Duffin ◽  
Michael Delbuono ◽  
Lawrence Chew ◽  
James Johnstone ◽  
Volker Niedan ◽  
...  
Keyword(s):  
Vaccine Development ◽  
Oral Vaccine ◽  
Storage Conditions ◽  
Hot Water ◽  
World Health ◽  
Self Administration ◽  
Health Agencies ◽  
Oral Cholera Vaccine ◽  
The Stability ◽  
User Friendly

ABSTRACTVaccination is a well-established means for prevention and spread of disease in people traveling abroad. Although vaccines to diseases such as cholera are recommended by world health agencies, they are seldom required even when traveling to endemic regions. Consequences of noncompliance can affect traveler’s health and spread diseases to new regions, as occurred in Haiti in 2010 when United Nations peacekeepers from Nepal, where a cholera outbreak was underway, introduced the disease to the region. Steps to increase vaccine recommendation compliance should therefore be an integral part of vaccine development. PXVX0200 contains Center for Vaccine Development 103-HgR live, attenuated recombinant Vibrio cholerae vaccine strain, and is indicated for single-dose immunization against the bacteria that causes cholera. It is supplied as one buffer and one active component packet to be mixed into water and ingested. Administration instructions are designed to be “user friendly” with flexibility for self-administration, thus promoting compliance. Studies to support self-administration were conducted to cover stability of the vaccine outside of normal storage conditions, potency in case of misadministration, and disposal procedures to minimize environmental impact. The principal findings showed that the stability of vaccine was maintained under conditions allowing for transport times and temperature conditions as well as when misadministration errors were made. Finally, the vaccine was effectively neutralized with hot water and soap to prevent bacterial environmental contamination in the event of an accidental spill. The conclusion is that PXVX0200 oral vaccine is stable, easy to formulate and dispose of, and is amenable to self-administration.

scholarly journals VACCINE DEVELOPMENT & MODERN APPROACHES FOR COVID 19

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.

scholarly journals Vaccines against enteric infections for the developing world

2015 ◽  
Vol 370 (1671) ◽  
pp. 20150142 ◽  
Author(s):  
Cecil Czerkinsky ◽  
Jan Holmgren
Keyword(s):  
Vaccine Development ◽  
Oral Vaccine ◽  
Herd Immunity ◽  
Oral Polio Vaccine ◽  
Developed Countries ◽  
Mucosal Vaccine ◽  
List Type ◽  
Limited Knowledge ◽  
Enteric Infections ◽  
Mucosal Vaccines

Since the first licensure of the Sabin oral polio vaccine more than 50 years ago, only eight enteric vaccines have been licensed for four disease indications, and all are given orally. While mucosal vaccines offer programmatically attractive tools for facilitating vaccine deployment, their development remains hampered by several factors: — limited knowledge regarding the properties of the gut immune system during early life; — lack of mucosal adjuvants, limiting mucosal vaccine development to live-attenuated or killed whole virus and bacterial vaccines; — lack of correlates/surrogates of mucosal immune protection; and — limited knowledge of the factors contributing to oral vaccine underperformance in children from developing countries. There are now reasons to believe that the development of safe and effective mucosal adjuvants and of programmatically sound intervention strategies could enhance the efficacy of current and next-generation enteric vaccines, especially in lesser developed countries which are often co-endemic for enteric infections and malnutrition. These vaccines must be safe and affordable for the world's poorest, confer long-term protection and herd immunity, and must be able to contain epidemics.

scholarly journals Self-assembling SARS-CoV-2 nanoparticle vaccines targeting the S protein induces protective immunity in mice

2021 ◽  
Author(s):  
Xingjian Liu ◽  
Haozhi Song ◽  
Jianmin Jiang ◽  
Xintao Gao ◽  
Yongzhu Yi ◽  
...  
Keyword(s):  
Development Strategy ◽  
Vaccine Development ◽  
Low Cost ◽  
Oral Vaccine ◽  
Expression System ◽  
Subcutaneous Administration ◽  
Baculovirus Expression System ◽  
Potential Candidate ◽  
S Protein ◽  
Assembly Technology

AbstractThe spike (S), a homotrimer glycoprotein, is the most important antigen target in the research and development of SARS-CoV-2 vaccine. There is no doubt that fully simulating the advanced structure of this homotrimer in the subunit vaccine development strategy is the most likely way to improve the immune protective effect of the vaccine. In this study, the preparation strategies of S protein receptor-binding domain (RBD) trimer, S1 region trimer, and ectodomain (ECD) trimer nanoparticles were designed based on ferritin nanoparticle self-assembly technology. The Bombyx mori baculovirus expression system was used to prepare these three nanoparticle vaccines with high expression levels in the silkworm. The immune results of mice show that the nanoparticle vaccine prepared by this strategy can not only induce an immune response by subcutaneous administration but also effective by oral administration. Given the stability of these ferritin-based nanoparticles vaccine, easy-to-use and low-cost oral immunization strategy can make up for the vaccination blind areas caused by the shortage of ultralow-temperature equipment and medical resources in underdeveloped areas. And the oral vaccine is also a very potential candidate to cut off the spread of SARS-CoV-2 in domestic and farmed animals, especially in stray and wild animals.

scholarly journals Expression of a Functional Single-Chain Variable-Fragment Antibody against Complement Receptor 1 in Streptococcus gordonii

2008 ◽  
Vol 15 (6) ◽  
pp. 925-931 ◽  
Author(s):  
Jennifer B. Knight ◽  
Scott A. Halperin ◽  
Kenneth A. West ◽  
Song F. Lee
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Vaccine Development ◽  
Oral Vaccine ◽  
Complement Receptor ◽  
Streptococcus Gordonii ◽  
Single Chain Variable Fragment ◽  
Single Chain ◽  
Complement Receptor 1

ABSTRACT Streptococcus gordonii, an oral commensal organism, is a candidate vector for oral-vaccine development. Previous studies have shown that recombinant S. gordonii expressing heterologous antigens was weakly immunogenic when delivered intranasally. In this study, antigen was specifically targeted to antigen-presenting cells (APC) in order to potentiate antigen-APC interactions and increase the humoral immune response to the antigen. To achieve this goal, a single-chain variable-fragment (scFv) antibody against complement receptor 1 (CR1) was constructed. Anti-CR1 scFv purified from Escherichia coli was able to bind to mouse mixed lymphocytes and bone marrow-derived dendritic cells. The in vivo function of the anti-CR1 scFv protein was assessed by immunizing mice intranasally with soluble scFv and determining the immune response against the hemagglutinin (HA) peptide located on the carboxy terminus of the scFv. The serum anti-HA immunoglobulin G (IgG) immune response was dose dependent; as little as 100 ng of anti-CR1 scFv induced a significant IgG immune response, while such a response was minimal when the animals were given an unrelated scFv. The anti-CR1 scFv was expressed in S. gordonii as a secreted protein, which was functional, as it bound to dendritic cells. Mice orally colonized by the anti-CR1-secreting S. gordonii produced an anti-HA IgG immune response, indicating that such an approach can be used to increase the immune response to antigens produced by this bacterium.

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