Assembly, Biochemical Characterization, Immunogenicity, Adjuvanticity, and Efficacy ofShigellaArtificial Invaplex

ABSTRACTThe native Invaplex (InvaplexNAT) vaccine and adjuvant is an ion exchange-purified product derived from the water extract of virulentShigellaspecies. The key component of InvaplexNATis a high-molecular-mass complex (HMMC) consisting of theShigellalipopolysaccharide (LPS) and the invasin proteins IpaB and IpaC. To improve product purity and immunogenicity, artificial Invaplex (InvaplexAR) was developed using recombinant IpaB and IpaC proteins and purifiedShigellaLPS to assemble an HMMC consisting of all three components. Characterization of InvaplexARby various methods demonstrated similar characteristics as the previously reported HMMC in InvaplexNAT. The well-defined InvaplexARvaccine consistently contained greater quantities of IpaB, IpaC, and LPS than InvaplexNAT. InvaplexARand InvaplexNATimmunogenicities were compared in mouse and guinea pig dose escalation studies. In both models, immunization induced antibody responses specific for InvaplexNATand LPS while InvaplexARinduced markedly higher anti-IpaB and -IpaC serum IgG and IgA endpoint titers. In the murine model, homologous protection was achieved with 10-fold less InvaplexARthan InvaplexNATand mice receiving InvaplexARlost significantly less weight than mice receiving the same amount of InvaplexNAT. Moreover, mice immunized with InvaplexARwere protected from challenge with both homologous and heterologousShigellaserotypes. Guinea pigs receiving approximately 5-fold less InvaplexARcompared to cohorts immunized with InvaplexNATwere protected from ocular challenge. Furthermore, adjuvanticity previously attributed to InvaplexNATwas retained with InvaplexAR. The second-generationShigellaInvaplex vaccine, InvaplexAR, offers significant advantages over InvaplexNATin reproducibility, flexible yet defined composition, immunogenicity, and protective efficacy.IMPORTANCEShigellaspecies are bacteria that cause severe diarrheal disease worldwide, primarily in young children. Treatment of shigellosis includes oral fluids and antibiotics, but the high burden of disease, increasing prevalence of antibiotic resistance, and long-term health consequences clearly warrant the development of an effective vaccine. OneShigellavaccine under development is termed the invasin complex or Invaplex and is designed to drive an immune response to specific antigens of the bacteria in an effort to protect an individual from infection. The work presented here describes the production and evaluation of a new generation of Invaplex. The improved vaccine stimulates the production of antibodies in immunized mice and guinea pigs and protects these animals fromShigellainfection. The next step in the product’s development will be to test the safety and immune response induced in humans immunized with Invaplex.

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Oral Peptide Vaccine against Hookworm Infection: Correlation of Antibody Titers with Protective Efficacy

Vaccines ◽

10.3390/vaccines9091034 ◽

2021 ◽

Vol 9 (9) ◽

pp. 1034

Author(s):

Ahmed O. Shalash ◽

Luke Becker ◽

Jieru Yang ◽

Paul Giacomin ◽

Mark Pearson ◽

...

Keyword(s):

Immune Response ◽

Worm Burden ◽

Vaccine Development ◽

Protective Efficacy ◽

Digestive Enzyme ◽

Peptide Vaccine ◽

Effective Vaccine ◽

Antigen Delivery ◽

Hookworm Infection ◽

Linear Arrangement

Approximately 0.4 billion individuals worldwide are infected with hookworm. An effective vaccine is needed to not only improve the health of those affected and at high risk, but also to improve economic growth in disease-endemic areas. An ideal anti-hookworm therapeutic strategy for mass administration is a stable and orally administered vaccine. Oral vaccines are advantageous as they negate the need for trained medical staff for administration and do not require strict sterility conditions. Vaccination, therefore, can be carried out at a significantly reduced cost. One of the most promising current antigenic targets for hookworm vaccine development is the aspartic protease digestive enzyme (APR-1). Antibody-mediated neutralization of APR-1 deprives the worm of nourishment, leading to reduced worm burdens in vaccinated hosts. Previously, we demonstrated that, when incorporated into vaccine delivery systems, the APR-1-derived p3 epitope (TSLIAGPKAQVEAIQKYIGAEL) was able to greatly reduce worm burdens (≥90%) in BALB/c mice; however, multiple, large doses of the vaccine were required. Here, we investigated a variety of p3-antigen conjugates to optimize antigen delivery and establish immune response/protective efficacy relationships. We synthesized, purified, and characterized four p3 peptide-based vaccine candidates with: (a) lipidic (lipid core peptide (LCP)); (b) classical polymeric (polymethylacrylate (PMA)); and (c) novel polymeric (polyleucine in a branched or linear arrangement, BL10 or LL10, respectively) groups as self-adjuvanting moieties. BL10 and LL10 induced the highest serum anti-p3 and anti-APR-1 IgG titers. Upon challenge with rodent hookworms, the highest significant reduction in worm burden was observed in mice immunized with LL10. APR-1-specific serum IgG titers correlated with worm burden reduction. Thus, we provide the first vaccine-triggered immune response-protection relationship for hookworm infection.

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Immunogenicity and protective efficacy of BBV152: a whole virion inactivated SARS CoV-2 vaccine in the Syrian hamster model

10.21203/rs.3.rs-76768/v1 ◽

2020 ◽

Cited By ~ 1

Author(s):

Sreelekshmy Mohandas ◽

Pragya D Yadav ◽

Anita Shete ◽

Priya Abraham ◽

Krishna Mohan ◽

...

Keyword(s):

Immune Response ◽

Respiratory Tract ◽

Neutralizing Antibodies ◽

Protective Efficacy ◽

Effective Vaccine ◽

Lung Pathology ◽

Upper Respiratory Tract ◽

Hamster Model ◽

Humoral Immune ◽

Robust Immune Response

Abstract The availability of a safe and effective vaccine would be the eventual measure to deal with SARS-CoV-2 threat. Here, we have developed and assessed the immunogenicity and protective efficacy of an inactivated SARS-CoV-2 vaccine (BBV152) in hamsters. Three dose vaccination regime with three formulations of BBV152 induced significant titres of SARS-CoV-2 specific IgG and neutralizing antibodies. The formulation with imidazoquinoline adsorbed on alum adjuvant remarkably generated a quick and robust immune response. Th1 biased immune response was demonstrated by the detection of IgG2 antibodies. Post-SARS-CoV-2 infection, vaccinated hamsters did not show any histopathological changes in the lungs. The protection of the hamsters was evident by the rapid clearance of the virus from lower respiratory tract, reduced virus load in upper respiratory tract, absence of lung pathology and robust humoral immune response. These findings confirm the immunogenic potential of BBV152 and further protection of hamsters challenged with SARS-CoV-2.

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Protection against SHIV-KB9 Infection by Combining rDNA and rFPV Vaccines Based on HIV Multiepitope and p24 Protein in Chinese Rhesus Macaques

Clinical and Developmental Immunology ◽

10.1155/2012/958404 ◽

2012 ◽

Vol 2012 ◽

pp. 1-9 ◽

Cited By ~ 7

Author(s):

Chang Li ◽

Zhenwei Shen ◽

Xiao Li ◽

Jieying Bai ◽

Lin Zeng ◽

...

Keyword(s):

Immune Response ◽

Viral Load ◽

Protective Efficacy ◽

Specific Binding ◽

Rhesus Macaques ◽

The Body ◽

Effective Vaccine ◽

Preclinical Research ◽

Aids Vaccine ◽

Chinese Rhesus Macaques

Developing an effective vaccine against HIV infection remains an urgent goal. We used a DNA prime/fowlpox virus boost regimen to immunize Chinese rhesus macaques. The animals were challenged intramuscularly with pathogenic molecularly cloned SHIV-KB9. Immunogenicity and protective efficacy of vaccines were investigated by measuring IFN-γlevels, monitoring HIV-specific binding antibodies, examining viral load, and analyzing CD4/CD8 ratio. Results show that, upon challenge, the vaccine group can induce a strong immune response in the body, represented by increased expression of IFN-γ, slow and steady elevated antibody production, reduced peak value of acute viral load, and increase in the average CD4/CD8 ratio. The current research suggests that rapid reaction speed, appropriate response strength, and long-lasting immune response time may be key protection factors for AIDS vaccine. The present study contributes significantly to AIDS vaccine and preclinical research.

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Humoral and cellular immune response to a crude exo-antigen and purified keratinase of Microsporum canis in experimentally infected guinea pigs

Medical Mycology ◽

10.1046/j.1365-280x.1999.00204.x ◽

1999 ◽

Vol 37 (2) ◽

pp. 123-129 ◽

Cited By ~ 4

Author(s):

B. R. Mignon ◽

T. Leclipteux ◽

CH. Focant ◽

A. J. Nikkels ◽

G. E. PIErard ◽

...

Keyword(s):

Immune Response ◽

Cellular Immune Response ◽

Guinea Pigs ◽

Microsporum Canis ◽

Cellular Immune

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Strategies for Vaccination: Conventional Vaccine Approaches Versus New-Generation Strategies in Combination with Adjuvants

Pharmaceutics ◽

10.3390/pharmaceutics13020140 ◽

2021 ◽

Vol 13 (2) ◽

pp. 140

Author(s):

Abdellatif Bouazzaoui ◽

Ahmed A. H. Abdellatif ◽

Faisal A. Al-Allaf ◽

Neda M. Bogari ◽

Saied Al-Dehlawi ◽

...

Keyword(s):

Viral Vectors ◽

Protein Production ◽

Vaccine Development ◽

Effective Vaccine ◽

The Novel ◽

Research Teams ◽

Advantages And Disadvantages ◽

Rapid Spread ◽

New Generation ◽

Conventional Vaccine

The current COVID-19 pandemic, caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), has raised significant economic, social, and psychological concerns. The rapid spread of the virus, coupled with the absence of vaccines and antiviral treatments for SARS-CoV-2, has galvanized a major global endeavor to develop effective vaccines. Within a matter of just a few months of the initial outbreak, research teams worldwide, adopting a range of different strategies, embarked on a quest to develop effective vaccine that could be effectively used to suppress this virulent pathogen. In this review, we describe conventional approaches to vaccine development, including strategies employing proteins, peptides, and attenuated or inactivated pathogens in combination with adjuvants (including genetic adjuvants). We also present details of the novel strategies that were adopted by different research groups to successfully transfer recombinantly expressed antigens while using viral vectors (adenoviral and retroviral) and non-viral delivery systems, and how recently developed methods have been applied in order to produce vaccines that are based on mRNA, self-amplifying RNA (saRNA), and trans-amplifying RNA (taRNA). Moreover, we discuss the methods that are being used to enhance mRNA stability and protein production, the advantages and disadvantages of different methods, and the challenges that are encountered during the development of effective vaccines.

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A Summary of the Third Global Interferon-γ Release Assay Symposium

Infection Control and Hospital Epidemiology ◽

10.1086/670634 ◽

2013 ◽

Vol 34 (6) ◽

pp. 619-624 ◽

Cited By ~ 2

Author(s):

Antonino Catanzaro ◽

Charles Daley

Keyword(s):

Immune Response ◽

Tuberculin Skin Test ◽

Skin Test ◽

Interferon Γ ◽

Enzyme Linked Immunosorbent Assay ◽

In Vitro Tests ◽

The Third ◽

Specific Antigens ◽

Ifn Γ

Studies over the past several decades have dramatically increased our understanding of the immune response to Mycobacterium tuberculosis infection, and advances in proteomics and genomics have led to a new class of immune-diagnostic tests, termed interferon-γ (IFN-γ) release assays (IGRAs), which appear to obviate many of the problems encountered with the tuberculin skin test (TST). Worldwide, 2 IGRAs are currently commercially available. QuantiFERON-TB Gold In-Tube (Cellestis) is a third-generation product that uses an enzyme-linked immunosorbent assay to measure IFN-γ generated in whole blood stimulated with M. tuberculosis–specific antigens. T-Spot-TB (Oxford Immunotec) employs enzyme-linked immunosorbent spot technology to enumerate the number of purified lymphocytes that respond to M. tuberculosis–specific antigens by producing IFN-γ. These in vitro tests measure the host immune response to M. tuberculosis–specific antigens, which virtually eliminates false-positive cross reactions caused by bacillus Calmette-Guérin vaccination and/or exposure to environmental nontuberculous mycobacteria that plague the interpretation and accuracy of the tuberculin skin test (TST). The high specificity of IGRAs, together with sensitivity commensurate with or better than that of the TST, promises an accurate diagnosis and the ability to focus tuberculosis-control activities on those who are actually infected with M. tuberculosis. The Third Global Symposium was held over a 3-day period and was presented by the University of California, San Diego, Continuing Medical Education department; slides and sound recordings of each presentation are available at http://cme.ucsd.edu/igras/syllabus.html. A moderated discussion is also available at http://cme.ucsd.edu/igrasvideo. This document provides a summary of the key findings of the meeting, specifically focusing on the use of IGRAs in screening healthcare worker populations.

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