Modern Vaccinology Research Articles

Liposome and polymer-based nanomaterials for vaccine applications

Nanoparticles (NPs) are effective and safe adjuvants for antigen delivery in modern vaccinology. Biodegradable nanomaterials with suitable properties are frequently applied for conjugation or loading with antigens; they protect the antigens from degradation in vivo. NPs are applied as effective delivery system to facilitate antigen uptake by antigen presenting cells (APCs) and especially dendritic cells (DCs) both in vitro and in vivo. Using nanoparticles to target DCs is an effective method to deliver antigens and potent immunomodulators. Uptake of NPs by DCs enhances the intracellular process of antigens and the antigen presentation pathway by MHC class I and II molecules to induce both CD4+ and CD8+ T-cell responses. Liposome and polymer-based NPs are now extensively applied as effective adjuvants or immunomodulators in several types of vaccines. In this review, the nanomaterials for vaccine application are focused intensively in poly(lactic-co-glycolic) acid (PLGA), dendrimers, liposomes, nanogels and micelles which are the targeted antigen delivery system, and present high potential as a promising future strategy for DNA-based, bacterial and viral vaccines. Further advances in nanotechnology and molecular immunology techniques will enhance the success of targeting and lead to the next generation of nano-delivery systems.

Immunogenicity and Immunodominance in Antibody Responses.

A large number of vaccines exist that control many of the most important infectious diseases. Despite these successes, there remain many pathogens without effective prophylactic vaccines. Notwithstanding strong difference in the biology of these infectious agents, there exist common problems in vaccine design. Many infectious agents have highly variable surface antigens and/or unusually high antibody levels are required for protection. Such high variability may be addressed by using conserved epitopes and these are, however, usually difficult to display with the right conformation in an immunogenic fashion. Exceptionally high antibody titers may be achieved using life vectors or virus-like display of the epitopes. Hence, an important goal in modern vaccinology is to induce high antibody responses against fragile antigens.

Konvencionalni i napredni adjuvansi u formulacijama vakcina - mineralni adsorbenti, nanočestični nosači i sistemi tipa mikroigala

In the era of modern vaccinology, limited immunogenicity of the most commonly used antigens has enforced the use of various adjuvants in vaccine formulations to achieve desired immune response. Aluminum-containing adjuvants have been, historically, the most widely used mineral immunostimulants, generally regarded as safe to use in human vaccines. The great academic progress in inorganic (nano)materials synthesis, structure control and functionalization design has led to a growing interest in innovative adjuvants such as clays, mesoporous silica nanoparticles, zinc oxide, iron oxide and iron hydroxide nanoparticles, etc. On the other hand, there has been an intention to use specific nanoparticulated antigen delivery systems, such as nanoemulsions, in order to protect antigens from premature proteolytic degradation and/or to improve antigen immunogenicity by facilitating antigen uptake and processing by antigen presenting cells. Simultaneously, numerous research efforts have been focused on the development of innovative technologies for antigen delivery into the skin (such as microneedles), with the aim to improve vaccine efficacy alongside with enhanced patient adherence, particularly in children population (noninvasive or minimally invasive administration). Therefore, this review deals with each of these approaches in more detail, with the special emphasis on examples of their use in vaccine formulations as well as on the factors influencing their efficacy and safety.

A Preliminary Study of a Lettuce-Based Edible Vaccine Expressing the Cysteine Proteinase of Fasciola hepatica for Fasciolosis Control in Livestock.

Oral vaccination with edible vaccines is one of the most promising approaches in modern vaccinology. Edible vaccines are an alternative to conventional vaccines, which are typically delivered by injection. Here, freeze-dried transgenic lettuce expressing the cysteine proteinase of the trematode Fasciola hepatica (CPFhW) was used to orally vaccinate cattle and sheep against fasciolosis, which is the most important trematode disease due to the parasite's global distribution, wide spectrum of host species and significant economic losses of farmers. In the study, goals such as reducing the intensity of infection, liver damage and F. hepatica fecundity were achieved. Moreover, we demonstrated that the host sex influenced the outcome of infection following vaccination, with female calves and male lambs showing better protection than their counterparts. Since differences occurred following vaccination and infection, different immunization strategies should be considered for different sexes and host species when developing new control methods. The results of the present study highlight the potential of oral vaccination with plant-made and plant-delivered vaccines for F. hepatica infection control.

INFLUENCE OF BRUCELLA ABORTUS I-206 THERMOEXTRACTS IN L- AND S-FORM ON MORPHOFUNCTIONAL STATE OF WHITE MICE ADRENAL GLANDS

Live vaccines are used for specific brucellosis prophylaxis in the Russian Federation. These vaccines in addition to a number of positive properties have some limitations including high agglutinogenicity, reactogenicity, sensitizing activity. In this connection, the development of subunit vaccines without adverse reactions is a perspective direction in modern vaccinology. Complex morphological research of the adrenal glands and comparative analysis of peripheral blood (leukogram, leukocytic index and index of allergization) of white mice immunized with thermoextracts (ТE) of Brucella abortus I-206 in L- and S-form and inactivated vaccine B. abortus 19 ВА were conducted. It was shown that ТE unlike B. abortus 19 ВА caused minor alterations in peripheral blood of the experimental animals in early periods of observation (increase of allergization index, changes in leukogram) with the subsequent levelling to the values in control. Expositions of the adrenal gland zoning were determined and cellular structure was estimated in consideration of morphometry. Changes in architectonics of the mice organ immunized with B. abortus 19 ВА were revealed. These alterations could indicate the stress-reaction development. In case of ТE application the given changes were insignificant and were developed in early periods. The revealed morphological changes in adrenal glands of laboratory animals permit to prove the necessity of realization the further experimental researches to ТE application as the components for development of a subcellular brucellosis vaccine.

Targeting Pattern Recognition Receptors (PRR) for Vaccine Adjuvantation: From Synthetic PRR Agonists to the Potential of Defective Interfering Particles of Viruses.

Modern vaccinology has increasingly focused on non-living vaccines, which are more stable than live-attenuated vaccines but often show limited immunogenicity. Immunostimulatory substances, known as adjuvants, are traditionally used to increase the magnitude of protective adaptive immunity in response to a pathogen-associated antigen. Recently developed adjuvants often include substances that stimulate pattern recognition receptors (PRRs), essential components of innate immunity required for the activation of antigen-presenting cells (APCs), which serve as a bridge between innate and adaptive immunity. Nearly all PRRs are potential targets for adjuvants. Given the recent success of toll-like receptor (TLR) agonists in vaccine development, molecules with similar, but additional, immunostimulatory activity, such as defective interfering particles (DIPs) of viruses, represent attractive candidates for vaccine adjuvants. This review outlines some of the recent advances in vaccine development related to the use of TLR agonists, summarizes the current knowledge regarding DIP immunogenicity, and discusses the potential applications of DIPs in vaccine adjuvantation.

Lactic acid bacteria - promising vaccine vectors: possibilities, limitations, doubts.

SummaryGram‐positive, nonpathogenic lactic acid bacteria (LAB) are considered to be promising candidates for the development of novel, safe production and delivery systems of heterologous proteins. Recombinant LAB strains were shown to elicit specific systemic and mucosal immune responses against selected antigens. For this reason, this group of bacteria is considered as a potential replacement of classical, often pathogenic, attenuated microbial carriers. Mucosal administration of recombinant LAB, especially via the best explored and universal oral route, offers many advantages in comparison to systemic inoculation, and is attractive from the immunological and practical point of view. Research aimed at designing efficient, mucosally applied vaccines in combination with improved immunization efficiency, monitoring of in vivo antigen production, determination of optimal dose for vaccination, strain selection and characterization is a priority in modern vaccinology. This paper summarizes and organizes the available knowledge on the application of LAB as live oral vaccine vectors. It constitutes a valuable source of general information for researchers interested in mucosal vaccine development and constructing LAB strains with vaccine potential.

Viral vaccines and their manufacturing cell substrates: New trends and designs in modern vaccinology.

Vaccination is one of the most effective interventions in global health. The worldwide vaccination programs significantly reduced the number of deaths caused by infectious agents. A successful example was the eradication of smallpox in 1979 after two centuries of vaccination campaigns. Since the first variolation administrations until today, the knowledge on immunology has increased substantially. This knowledge combined with the introduction of cell culture and DNA recombinant technologies revolutionized vaccine design. This review will focus on vaccines against human viral pathogens, recent developments on vaccine design and cell substrates used for their manufacture. While the production of attenuated and inactivated vaccines requires the use of the respective permissible cell substrates, the production of recombinant antigens, virus‐like particles, vectored vaccines and chimeric vaccines requires the use – and often the development – of specific cell lines. Indeed, the development of novel modern viral vaccine designs combined with, the stringent safety requirements for manufacture, and the better understanding on animal cell metabolism and physiology are increasing the awareness on the importance of cell line development and engineering areas. A new era of modern vaccinology is arriving, offering an extensive toolbox to materialize novel and creative ideas in vaccine design and its manufacture.

Trends in vaccinology education of nurses in Poland

Introduction. The tangible result of the successful implementation of immunoprophylaxis is properly organized and conducted education on vaccinology of parents and people to be vaccinated, which should be carried out by medical professionals of different specialties, including nurses performing vaccinations. Aim. Presentation of trends in the development of vaccinology education of nurses in Poland. Material and methods. Overview of Polish and foreign medical literature in the years 2000-2014 on education of society by medical personnel in the field of active immunization. Results. Changes in the immunoprophylaxis in Poland, the aim of which is further development of Immunization Program in accordance with trends in many European countries, necessitate ongoing vaccinology education. This requires from the medical staff (a doctor and a nurse) not only current knowledge about vaccination, but also the ability to communicate effectively and build a feeling of trust in the relationship with patients. The theoretical foundation of modern vaccinology education should be viewing it as a process, the outcome of which is to achieve competences of the trainee to express judgments and make effective decisions on matters related to immunization. Conclusions. 1 . Educational activities of medical personnel in the field of immunization are crucial for the social acceptance of this method of infectious diseases prevention. 2. Effective implementation of vaccinology education by medical personnel requires continuing professional and personal development as well as interpersonal communication skills. 3. Appointment of the vaccinology educators and interdisciplinary method of implementation of education on vaccination may be a desirable trend in the development of active immunization.

New challenges in modern vaccinology.

Vaccination has been a major advance for health care, allowing eradication or reduction of incidence and mortality of various infectious diseases. However, there are major pathogens, such as Human Immunodeficiency Virus (HIV) or the causative agent of malaria, for which classical vaccination approaches have failed, therefore requiring new vaccination strategies. The development of new vaccine strategies relies on the ability to identify the challenges posed by these pathogens. Understanding the pathogenesis and correlates of protection for these diseases, our ability to accurately direct immune responses and to vaccinate specific populations are such examples of these roadblocks. In this respect, the use of a robust, cost-effective and predictive animal model that recapitulates features of both human infection and vaccination is currently a much-needed tool. We discuss here the major limitations faced by modern vaccinology and notably, the development of humanized mice for assessing the immune system, along with their potential as vaccine models.

Next generation vaccines: single-dose encapsulated vaccines for improved global immunisation coverage and efficacy.

Vaccination is considered the most successful health intervention; yet incomplete immunisation coverage continues to risk outbreaks of vaccine preventable diseases worldwide. Vaccination coverage improvement through a single-dose prime-boost technology would revolutionise modern vaccinology, impacting on disease prevalence, significantly benefiting health care and lowering economic burden of disease. Over the past 30 years, there have been efforts to develop a single-dose delayed release vaccine technology that could replace the repeated prime-boost immunisations required for many current vaccines. Biocompatible polymers have been employed to encapsulate model vaccines for delayed delivery in vivo, using either continuous or pulsed release. Biomaterial considerations, safety aspects, particle characteristics and immunological aspects of this approach are discussed in detail. Despite many studies showing the feasibility of vaccine encapsulation for single-dose prime-boost administration, none have been translated into convincing utility in animal models or human trials. Further development of the encapsulation technology, through optimising the particle composition, formulation, antigen loading efficacy and stability, could lead to the application of this important approach in vaccine deployment. If successful, this would provide a solution to better global vaccination coverage through a reduction in the number of immunisations needed to achieve protection against infectious diseases. This review provides an overview of single-dose vaccination in the context of today's vaccine needs and is derived from a body of literature that has not been reviewed for over a decade.

Modified Vaccinia Virus Ankara as Vaccine Vectors in Human and Veterinary Medicine

ABSTRACT: Disease prevention through vaccination is one of the most important achievements of medicine. Today, we have a substantial number of vaccines against a variety of pathogens. In this context, poxviruses and vaccinology are closely related, as the birth of modern vaccinology was marked by the use of poxviruses as immunogens and so was the eradication of smallpox, one of the world's most feared diseases ever. Nowadays, poxviruses continue to notoriously contribute to vaccinology since their use as vaccine vectors has become popular and widespread. One of the most promising vectors is the modified vaccinia ankara. In this review we provide an overview of the contribution of poxvirus to vaccine immunology, particularly focusing on modified vaccinia ankara-based vaccines developed to date.

Montanide ISA™ 201 adjuvanted FMD vaccine induces improved immune responses and protection in cattle

Despite significant advancements in modern vaccinology, inactivated whole virus vaccines for foot-and-mouth disease (FMD) remain the mainstay for prophylactic and emergency uses. Many efforts are currently devoted to improve the immune responses and protective efficacy of these vaccines. Adjuvants, which are often used to potentiate immune responses, provide an excellent mean to improve the efficacy of FMD vaccines. This study aimed to evaluate three oil adjuvants namely: Montanide ISA-201, ISA-206 (SEPPIC, France) and GAHOL (an in-house developed oil-adjuvant) for adjuvant potential in inactivated FMD vaccine. Groups of cattle (n=6) were immunized once intramuscularly with monovalent FMDV ‘O’ vaccine formulated in these adjuvants, and humoral (serum neutralizing antibody, IgG1 and IgG2) and cellular (lymphoproliferation) responses were measured. Montanide ISA-201 adjuvanted vaccine induced earlier and higher neutralizing antibody responses as compared to the two other adjuvants. All the adjuvants induced mainly serum IgG1 isotype antibody responses against FMDV. However, Montanide ISA-201 induced relatively higher IgG2 responses than the other two adjuvants. Lymphoproliferative responses to recall FMDV antigen were relatively higher with Montanide ISA-201, although not always statistically significant. On homologous FMDV challenge at 30 days post-vaccination, 100% (6/6) of the cattle immunized with Montanide-201 adjuvanted vaccine were protected, which was superior to those immunized with ISA-206 (66.6%, 4/6) or GAHOL adjuvanted vaccine (50%, 3/6). Virus replication following challenge infection, as determined by presence of the viral genome in oropharynx and non-structural protein serology, was lowest with Montanide ISA-201 adjuvant. Collectively, these results indicate that the Montanide ISA-201 adjuvanted FMD vaccine induces enhanced immune responses and protective efficacy in cattle.

Adjuvants are Key Factors for the Development of Future Vaccines: Lessons from the Finlay Adjuvant Platform

The development of effective vaccines against neglected diseases, especially those associated with poverty and social deprivation, is urgently needed. Modern vaccine technologies and a better understanding of the immune response have provided scientists with the tools for rational and safer design of subunit vaccines. Often, however, subunit vaccines do not elicit strong immune responses, highlighting the need to incorporate better adjuvants; this step therefore becomes a key factor for vaccine development. In this review we outline some key features of modern vaccinology that are linked with the development of better adjuvants. In line with the increased desire to obtain novel adjuvants for future vaccines, the Finlay Adjuvant Platform offers a novel approach for the development of new and effective adjuvants. The Finlay Adjuvants (AFs), AFPL (proteoliposome), and AFCo (cochleate), were initially designed for parenteral and mucosal applications, and constitute potent adjuvants for the induction of Th1 responses against several antigens. This review summarizes the status of the Finlay technology in producing promising adjuvants for unsolved-vaccine diseases including mucosal approaches and therapeutic vaccines. Ideas related to adjuvant classification, adjuvant selection, and their possible influence on innate recognition via multiple toll-like receptors are also discussed.

The Jenner Society and the Edward Jenner Museum: Tributes to a physician-scientist

Dr. Edward Jenner's discovery and application of vaccination against smallpox was one of the most important medical advances of all time. In the modern era many millions of lives are saved each year by vaccines that work essentially on the same scientific principles established by Jenner more than 200 years ago. Jenner's country home in Berkeley, Gloucestershire, UK, where he carried out his work and where he spent most of his life, is now a museum and something of a shrine for vaccinologists. Jenner's house is also now the focal point of a new international learned society dedicated to advancing modern vaccinology. The aims of the new Jenner Society are to engage, support, and sustain the professional goals of vaccinologists, and to perpetuate the memory of Dr. Edward Jenner. Ultimately it is hoped that the Jenner Society will be recognized as one of the leading academic societies representing and promoting vaccine science around the world. We invite readers to consider joining the society (http://www.edwardjennersociety.org/).

Cost Effectiveness of HPV Vaccine for Boys

Cost Effectiveness of HPV Vaccine for Boys

DNA vaccines: are they still just a powerful tool for the future?

Vaccination is historically one of the most successful strategies for the prevention of infectious diseases. For safety reasons, modern vaccinology tends toward the usage of inactivated or attenuated microorganisms and uses predominantly subunit vaccines. The antigens need to be clearly defined, pure, stable, appropriately composed, and properly presented to the immune system of the host. Differing ratios of various proportions between specific CD4+ and CD8+ T cell responses are essential for conferring the required protection in the case of individual vaccines. To stimulate both CD4+ and CD8+ T cells, the antigens must be processed and presented to both antigen-presentation pathways, MHC I and MHC II. Protein antigens delivered by vaccination are processed as extracellular antigens. However, extracellularly delivered antigen can be directed towards intracellular presentation pathways in conjugation with molecules involved in antigen cross-presentation, e.g. heat shock proteins, or by genomic-DNA vaccination. In this overview, current knowledge of the host immune response to DNA vaccines is summarized in the introduction. The subsequent sections discuss techniques for enhancing DNA vaccine efficacy, such as DNA delivery to specific tissues, delivery of DNA to the cell cytoplasm or nucleus, and enhancement of the immune response using molecular adjuvants. Finally, the prospects of DNA vaccination and ongoing clinical trials with various DNA vaccines are discussed.

The “Green Channel” of the Veneto region as a model for vaccine safety monitoring in Italy

Modern vaccinology and public health organizations need to satisfy an increased safety demand. Therefore, to improve adverse events following immunization (AEFIs) surveillance systems, some countries have established clinical evaluation centers for AEFI assessment and management of at risk individuals. In the Veneto region of Italy, the Green Channel operates through a counselling service for subjects with prior AEFI or with suspected contraindications to vaccine administration, and a surveillance system of the AEFIs reported in the region. Updated data on 753 consultations and 3023 AEFI analyses are discussed together with the opportunity to include the Green Channel model as part of an international vaccine safety network.

New approaches in vaccine development

In the last century, vaccines have been one of the most powerful tools for preventing infectious diseases. Smallpox has been eradicated and other diseases such as poliomyelitis or measles have been reduced to very low levels in many regions of the world. However, infectious diseases remain the leading cause of death worldwide. Thus, the development of vaccines to prevent diseases for which no vaccine currently exists such as AIDS or malaria as well as the improvement of efficacy and safety of existing vaccines remains a high priority. Achieving such ambitious goals in a near future will certainly require a strong modification of the methods that have been used so far to identify vaccine candidates. In particular, modern vaccinology could strongly benefit of the latest developments of molecular biology and immunology. Here, we will discuss some potential applications of the increasing knowledge of pathogen genomes as well as the immune system for the discovery of new antigenic targets and the development of new strategies of vaccination.

Recent progress in the development of vaccines for infants and children

Infectious agents do not respect national or international boundaries. Attempts to prevent their spread, and the diseases which they cause, involve implementing vaccination as widely and as appropriately as possible. The principles of vaccination against infectious agents are now being applied to cancer and other non-infectious conditions. In order to understand where modern vaccinology is heading, it is necessary to first examine individual components. This brief overview examines the following: Streptococcus pneumoniae, Neisseria meningitidis, varicella zoster, measles, rotavirus, HIV, influenza, “emerging” viral infections and cancer.