Modern Vaccinology Research Articles

Wuhan Sequence-Based Recombinant Antigens Expressed in E. coli Elicit Antibodies Capable of Binding with Omicron S-Protein.

The development of cross-reactive vaccines is one of the central aims of modern vaccinology. Continuous mutation and the emergence of new SARS-CoV-2 variants and subvariants create the problem of universal coronavirus vaccine design. Previously, the authors devised three recombinant coronavirus antigens, which were based on the sequence collected in 2019 (the Wuhan variant) and produced in an E. coli bacterial expression system. The present work has shown, for the first time, that these recombinant antigens induce the production of antibodies that clearly interact with produced in CHO full-length S-protein of the Omicron variant. The immunogenicity of these recombinant antigens was studied in formulations with different adjuvants: Freund's adjuvant, Al(OH)3 and an adjuvant based on spherical particles (SPs), which are structurally modified plant virus. All adjuvanted formulations effectively stimulated Omicron-specific IgG production in mice. These universal coronavirus antigens could be considered the main component for the further development of broad-spectrum coronavirus vaccines for the prevention of SARS-CoV-2 infection. The present work also provides evidence that the synthetic biology approach is a promising strategy for the development of highly cross-reactive vaccines. Moreover, it is important to note that the bacterial expression system might be appropriate for the production of antigenically active universal antigens.

Vaccinomics and adversomics: key elements for a personalized vaccinology.

Vaccines are one of the most important and effective tools in the prevention of infectious diseases and research about all the aspects of vaccinology are essential to increase the number of available vaccines more and more safe and effective. Despite the unquestionable value of vaccinations, vaccine hesitancy has spread worldwide compromising the success of vaccinations. Currently, the main purpose of vaccination campaigns is the immunization of whole populations with the same vaccine formulations and schedules for all individuals. A personalized vaccinology approach could improve modern vaccinology counteracting vaccine hesitancy and giving great benefits for human health. This ambitious purpose would be possible by facing and deepening the areas of vaccinomics and adversomics, two innovative areas of study investigating the role of a series of variables able to influence the immune response to vaccinations and the development of serious side effects, respectively. We reviewed the recent scientific knowledge about these innovative sciences focusing on genetic and non-genetic basis involved in the individual response to vaccines in terms of both immune response and side effects.

Poly(I:C), chitosan oligosaccharide, and chitosan enhance inactivated GCRV vaccine potency in grass carp Ctenopharyngodon idella

Vaccination is the most promising strategy to combat infectious diseases. Vaccine adjuvants are considered as key components in modern vaccinology since they provide the necessary help in enhancing the immune responses. This study evaluated the protective effects of poly (I:C), chitosan oligosaccharides (COS) and chitosan as new adjuvants in enhancing immune response and inhibiting GCRV replication using inactivated GCRV vaccines. Complete Freund's adjuvant (CFA) was used as a control adjuvant, and the survival rate of each group of grass carp was assessed. The CiIgM protein levels in sera were obviously boosted and sustained by the three novel adjuvant supplies, examining by enzyme-linked immunosorbent assay (ELISA) and western blotting (WB) methods. Meanwhile, mRNA expression of CiIgM in spleen and head kidney were elevated, checking by real time quantitative RT-PCR (qRT-PCR) assays. The Th1, not Th2 type immune responses, pro-inflammation cytokines and innate antiviral genes were also reinforced in spleen and head kidney tissues at early stages. The GCRV replication was significantly reduced post GCRV injection. The tissue sectioning showed a significant reduction in tissue damage in muscles, intestines, and hepatopancreatic tissues under the protection of the three adjuvants. The results indicated that poly(I:C), COS and chitosan can serve as novel and efficient adjuvants in inactivated vaccine in grass carp.

Immunoinformatics and tick vaccinology

Immunoinformatics is an emerging area focused on development and applications of methods used to facilitate vaccine development. There is a growing interest in the field of vaccinology centered on the new omic science named ‘vaccinomics’. However, this approach has not succeeded to provide a solution against major infections affecting both animals and humans, since tick vaccines are still being developed based on conventional biochemical or immunological methods to dissect the molecular structure of the pathogen, looking for a candidate antigen. The availability of complete genomes and the novel advanced technologies, such as data mining, bioinformatics, microarrays, and proteomics, have revolutionized the approach to vaccine development and provided a new impulse to tick research. The aim of this review is to explore how modern vaccinology will contribute to the discovery of new candidate antigens and to understand the research process to improve existing vaccines. Under this concept, the omic age of ticks will make it possible to design vaccines starting from a prediction based on the in silico analysis of gene sequences obtained by data mining using computer algorithms, without the need to keep the pathogen growing in vitro. This new genome-based approach has been named “reverse vaccinology 3.0” or “vaccinomics 1.0” and can be applied to ticks.

Recombinant vaccine candidates with integrated adjuvants provide stimulation of an effective immune response against bacterial infections

The use of recombinant proteins as vaccine preparations is limited by their weak immunogenicity, which can be enhanced by the use of adjuvants, the development of which is an important and urgent problem of modern vaccinology. Significantly, adjuvants as additives to vaccine preparations are of concern to clinicians. From this point of view, the idea of including an internal adjuvant into the structure of a recombinant protein molecule is of undoubted interest. Previously, we synthesized and studied two recombinant vaccine preparations specific for S. agalactiae (Su4) and S. pneumoniae (PSPF). Each of them was a tandem of immunogenic bacterial surface proteins in combination with an additional adjuvant site. The amino acid sequence identical to flagellin acted as an internal adjuvant. In this work, we investigated the possibility of additional enhancement of the body’s immune response to immunization with recombinant Su4 and PSPF proteins due to the simultaneous administration of an external adjuvant, carboxymethylchitosan or Imject Alum.Studies have shown that the additional introduction of these adjuvants into the composition of the vaccine preparation did not affect the immunogenicity of the Su4 and PSPF proteins, which included the internal adjuvant flagellin. The protective efficacy of the immune response to all immunization options was comparable.Thus, the inclusion of a flagellin insert as an internal adjuvant into the composition of recombinant proteins ensures the development of the highest possible level of the immune response and its protective efficacy against the corresponding pathogens of a bacterial infection.

Moderna (mRNA Vaccine) for COVID-19: A Leap in Vaccine World


 
 
 
 In December 2019, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) appeared and spread worldwide, triggering a pandemic of respiratory illness. So, there was an urgent need for vaccines worldwide. The mRNA-based vaccines are undergoing an accelerated phase of development during this pandemic. WHO has issued interim guidelines for administering the Moderna mRNA-1273 vaccine against COVID-19 based on advice given by the Strategic Advisory Group of Experts on Immunization (SAGE). The significant future directions for study would be comparing and elucidating the immune processes triggered by mRNA vaccine platforms, developing existing methods focused on these mechanisms, and introducing new clinical trials of these vaccines against additional disease targets.
 This study aims to reveal the important role and contribution of the Moderna mRNA-1273 vaccine to COVID-19 vaccinology.
 Moderna mRNA-1273 vaccine could be the keystone of modern vaccinology in the context of the COVID-19 pandemic.
 
 
 

Sticholysin II shows similar immunostimulatory properties to LLO stimulating dendritic cells and MHC-I restricted T cell responses of heterologous antigen

Induction of CD8+ T cell responses against tumor cells and intracellular pathogens is an important goal of modern vaccinology. One approach of translational interest is the use of liposomes encapsulating pore-forming proteins (PFPs), such as Listeriolysin O (LLO), which has shown efficacy at priming strong and sustained CD8+ T cell responses. Recently, we have demonstrated that Sticholysin II (StII), a PFP from the sea anemone Stichodactyla helianthus, co-encapsulated into liposomes with ovalbumin (OVA) was able to stimulate, antigen presenting cells, antigen-specific CD8+ T cells and anti-tumor activity in mice. In the present study, we aimed to compare StII and LLO in terms of their abilities to stimulate dendritic cells and to induce major histocompatibility complex (MHC) class I restricted T cell responses against OVA. Interestingly, StII exhibited similar abilities to LLO in vitro of inducing dendritic cells maturation, as measured by increased expression of CD40, CD80, CD86 and MHC-class II molecules, and of stimulating OVA cross-presentation to a CD8+ T cell line. Remarkably, using an ex vivo Enzyme-Linked ImmunoSpot Assay (ELISPOT) to monitor gamma interferon (INF-γ) producing effector memory CD8+ T cells, liposomal formulations containing either StII or LLO induced comparable frequencies of OVA-specific INF-γ producing CD8+ T cells in mice that were sustained in time. However, StII-containing liposomes stimulated antigen-specific memory CD8+ T cells with a higher potential to secrete IFN-γ than liposomes encapsulating LLO. This StII immunostimulatory property further supports its use for the rational design of T cell vaccines against cancers and intracellular pathogens. In summary, this study indicates that StII has immunostimulatory properties similar to LLO, despite being evolutionarily distant PFPs.

Current opportunities for vaccine prophylaxis of common infections in immunosuppressed adult patients

One of the slogans of modern clinical vaccinology is — “You have taken enough care of your children’s health, and now it is time to take care of yourselves and your parents — it is high time to think seriously about vaccinating adults!” It is indeed true that for a long time vaccinology has been confined to the paediatric service only, while general practitioners and specialists of the therapeutic branches of medicine have dealt with vaccination very rarely, and only in relation to seasonal influenza. This is often due to the fact that clinicians often have insufficient or inaccurate information regarding the need for and the effectiveness of vaccination in adult patients, including those with immunosuppression or comorbidity. In some cases, the infrastructure needed to develop a tailored vaccination schedule for adult patient groups at increased risk of developing infectious complications is lacking. This article presents current data with regard to vaccination of immunosuppressed adult patients.

VLP-Based Vaccines as a Suitable Technology to Target Trypanosomatid Diseases.

Research on vaccines against trypanosomatids, a family of protozoa that cause neglected tropical diseases, such as Chagas disease, leishmaniasis, and sleeping sickness, is a current need. Today, according to modern vaccinology, virus-like particle (VLP) technology is involved in many vaccines, including those undergoing studies related to COVID-19. The potential use of VLPs as vaccine adjuvants opens an opportunity for the use of protozoan antigens for the development of vaccines against diseases caused by Trypanosoma cruzi, Leishmania spp., and Trypanosoma brucei. In this context, it is important to consider the evasion mechanisms of these protozoa in the host and the antigens involved in the mechanisms of the parasite–host interaction. Thus, the immunostimulatory properties of VLPs can be part of an important strategy for the development and evaluation of new vaccines. This work aims to highlight the potential of VLPs as vaccine adjuvants for the development of immunity in complex diseases, specifically in the context of tropical diseases caused by trypanosomatids.

Vaccination through time: from the first smallpox vaccine to current vaccination campaigns against the COVID-19 pandemic.

The systematic study of the evolution of the concept of vaccination constitutes a fascinating journey through time and the scientific development of effective and safe vaccines against infectious diseases is one of the greatest achievements in the history of medicine. In the western world vaccination dates back to the eighteenth century, a period in which smallpox was a diffused and often lethal disorder, and in many countries attempts at the prevention of such a medical and social threat were conducted. The English surgeon Edward Jenner (1749-1823) is commonly considered the discoverer of the vaccination for smallpox. Moving from remote history to recent periods, the ongoing 2019-2021 coronavirus disease (COVID-19) pandemic has posed a tremendous challenge to the health systems of the countries involved. It has triggered all over the world the rapid development of several effective vaccines, never before prepared in such a brief span of time. It must be acknowledged that modern vaccinology as a science stands at the crossroads of multiple medical specialties and scientific disciplines. In turn, twentieth century explosive progress in the field of vaccination has triggered the development of other important medical areas, from immunopathology to infectious diseases therapy, and from prevention to anti-cancer treatment. Nowadays, effective and diffused control of infectious diseases cannot be done without vaccines, as the COVID-19 pandemic has once again demonstrated, and the role of well structured vaccine programs and of capillary and systematic vaccine campaigns has become central for the health of entire populations all over the world. (www.actabiomedica.it)

A tractable covalent linker strategy for the production of immunogenic antigen-TLR7/8L bioconjugates.

Despite the ease of production and improved safety profiles of recombinant vaccines, the inherently low immunogenicity of unadjuvanted proteins remains an impediment to their widespread adoption. The covalent tethering of TLR agonists to antigenic proteins offers a unique approach to co-deliver both constituents to the same cell–enhancing vaccine efficacy while minimizing reactogenicity. However, the paucity of simple and effective linker chemistries continues to hamper progress. Here, we present a modular, PEG-based linker system compatible with even extremely lipophilic and challenging TLR7/8 agonists. To advance the field and address previous obstacles, we offer the most straightforward and antigen-preserving linker system to date. These antigen-adjuvant conjugates enhance antigen-specific immune responses in mice, demonstrating the power of our approach within the context of modern vaccinology.

Modern Practices of Vaccination of Children from Perinatal Risk Groups and Necessary Precaution

Relevance. In perinatal centres problems of timely vaccination of newborns arise more often than in maternity hospitals, as vaccinations against viral hepatitis B and tuberculosis in accordance with the National Calendar are carried out in an early neonatal period and in time coincide with the stage of treatment and rehabilitation of the newborn, which implies medical withdrawal from vaccination. Vaccination of newborns from high perinatal risk groups is one of the problems of modern vaccinology and immunology.Aims. On the basis of clinical and immunological characteristics of postnatal babies from mothers with gestational diabetes and fetoplacental insufficiency justify the necessity and safety of their vaccination in the maternity hospital of the perinatal center.Materials & Methods. A cohort retrospective case-control study was conducted, and 135 birth and developmental history and newborn disease were analyzed. Statistical processing was carried out package «Statistica».Results. The main nosological forms of pathology in maternity mothers and their newborn children, the volume of primary vaccination (against viral hepatitis B, tuberculosis) in maternity hospital in children with perinatal pathology and healthy newborns have been determined, and the reasons for medical contraindications to vaccinations against viral hepatitis B and tuberculosis have been established.Conclusions. Newborns from high perinatal risk groups can be vaccinated against viral hepatitis B and tuberculosis in the maternity hospital within the time frame specified by the National Calendar of Preventive Vaccinations. In addressing this issue, the fundamental criteria are to assess the clinical condition of newborns from women with gestational diabetes and fetoplacental insufficiency. Changes in immunological values of umbilical cord blood and in children of 1 month of life are not a criterion for medical withdrawal from vaccinations against viral hepatitis B and tuberculosis.

In Silico Design of a Poly-epitope Vaccine for Urinary Tract Infection Based on Conserved Antigens by Modern Vaccinology

Immunoinformatics or vaccine informatics focuses on applying computational approaches to advance vaccine research and development (RD reverse translation and codon optimization; second and third structure predictions were utilized for both vaccine candidates. Finally, the designed constructs with particular conserved epitopes with linkers and carriers were structurally approved. These vaccine candidates could be used as a broad immune system inducer, and its cross-protective immunity in UTI would confirm in the future.

Still naïve or primed: Anticoccidial vaccines call for memory

Despite decades of investigation to clarify protective mechanisms of anticoccidial responses, one crucial field is neglected, that is, protective memory responses in primed birds. Protective memory immunity is critical for host resistance to reinfection and is the basis of modern vaccinology, especially in developing successful subunit vaccines. There are important differences between the immune responses induced by infections and antigens delivered either as killed, recombinant proteins or as live, replicating vector vaccines or as DNA vaccines. Animals immunized with these vaccines may fail to develop protective memory immunity, and is still naïve to Eimeria infection. This may explain why limited success is achieved in developing next-generation anticoccidial vaccines. In this review, we try to decipher the protective memory responses against Eimeria infection, assess immune responses elicited by various anticoccidial vaccine candidates, and propose possible approaches to develop rational vaccines that can induce a protective memory response to chicken coccidiosis.

Exploring the Prospects of Engineered Newcastle Disease Virus in Modern Vaccinology.

Many traditional vaccines have proven to be incapable of controlling newly emerging infectious diseases. They have also achieved limited success in the fight against a variety of human cancers. Thus, innovative vaccine strategies are highly needed to overcome the global burden of these diseases. Advances in molecular biology and reverse genetics have completely restructured the concept of vaccinology, leading to the emergence of state-of-the-art technologies for vaccine design, development and delivery. Among these modern vaccine technologies are the recombinant viral vectored vaccines, which are known for their incredible specificity in antigen delivery as well as the induction of robust immune responses in the vaccinated hosts. Although a number of viruses have been used as vaccine vectors, genetically engineered Newcastle disease virus (NDV) possesses some useful attributes that make it a preferable candidate for vectoring vaccine antigens. Here, we review the molecular biology of NDV and discuss the reverse genetics approaches used to engineer the virus into an efficient vaccine vector. We then discuss the prospects of the engineered virus as an efficient vehicle of vaccines against cancer and several infectious diseases of man and animals.

Polymer-based nanoadjuvants for hepatitis C vaccine: The perspectives of immunologists

The hepatitis C virus (HCV) is an infection that affects the liver tissues in humans, leading to the development of effective prophylactic and therapeutic HCV vaccines to prevent a global epidemic. Scientists consider it challenging to produce a therapeutic vaccine for the treatment of hepatocellular carcinoma as opposed to a preventative vaccine. However, several drawbacks are involved with a peptide vaccine, including the low immunogenicity of the protein, significant instability, difficulty in delivery, and inefficient presentation of the antigens. Therefore, the investigation of adjuvants (i.e., immunomodulators) to enhance the efficacy of the vaccine is essential. Nanoparticles could potentially serve as vaccine delivery vehicles, acting as adjuvants for the effective transfer of antigens. The safety and effectiveness of nanoparticles and liposomes in modern vaccinology have also been confirmed. Biodegradable nanopolymers such as polyesters, polylactic acid and the copolymers, polyorthoesters, polyanhydrides, and polycarbonates are commonly used owing to their proper qualities in the combination or loading for the prevention of the degradation of the delivered antigens. The present study is specifically focused on the polymer-based nanoparticles that are mostly comprised a poly (amino acid) based copolymer and poly (D, L-lactic-co-glycolide), which could act as adjuvants or potential immunomodulators for the systems providing effective HCV vaccine delivery.

Biomimetic nanoparticles as universal influenza vaccine

Pandemic virus infections pose a major public health threat globally. Much efforts have been devoted to suppress the virus, including vaccine prevention, autoimmunity enhancement, and anti-virus drugs treatment. Among these strategies, development of novel and improved vaccine technologies attracts broad attention as they can nip the virus outbreak in the bud and avoid the appearance of public health emergency. However, current influenza vaccines only provide protection against homologous viruses. Therefore, chemical technologies are being employed for the development of new and improved vaccine, such as chitosan, plant polysaccharides and virus-like particles. In addition, recently, Wang et al. offered a promising means to develop universal viral vaccine through biomimetic nanoparticles and heterosubtypic protection could be achieved. These strategies with multidisciplinary collaboration are promising to make conceptual and technological advances of modern vaccinology to address pandemic virus infections.

Vaccine Development against the Renin-Angiotensin System for the Treatment of Hypertension.

Hypertension is a global public health issue and the most important preventable cause of cardiovascular diseases. Despite the clinical availability of many antihypertensive drugs, many hypertensive patients have poor medication adherence and blood pressure control due, at least partially, to the asymptomatic and chronic characteristics of hypertension. Immunotherapeutic approaches have the potential to improve medication adherence in hypertension because they induce prolonged therapeutic effects and need a low frequency of administration. The first attempts to reduce blood pressure by using vaccines targeting the renin-angiotensin system were made more than half a century ago; however, at the time, a poor understanding of immunology and the mechanisms of hypertension and a lack of optimal vaccine technologies such as suitable antigen design, proper adjuvants, and effective antigen delivery systems meant that attempts to develop antihypertensive vaccines failed. Recent advances in immunology and vaccinology have provided potential therapeutic immunologic approaches to treat not only infectious diseases but also cancers and other noncommunicable diseases. One important biotechnology that has had a major impact on modern vaccinology is virus-like particle technology, which can efficiently deliver vaccine antigens without the need for artificial adjuvants. A human clinical trial that indicated the effectiveness and safety of a virus-like particle-based antiangiotensin II vaccine marked a turning point in the field of therapeutic antihypertensive vaccines. Here, we review the history of the development of immunotherapies for the treatment of hypertension and discuss the current perspectives in the field.

Vaccine Evolution and Its Application to Fight Modern Threats.

Before the development of the first vaccine, infectious diseases were a major cause of death around the globe with life expectancy estimated to be <50 years. Three measures have helped to drastically reduce the burden of infectious diseases but only vaccines have proven to be able to eradicate infectious agents. Herein, we describe new methodologies that have paved the way for what is currently known as modern vaccinology and the use of vaccines to tackle antimicrobial resistance, the biggest global threat of our time.

New Horizons of National Immunization Calendar

Containment, prevention and elimination of infectious disease is the state duty for citizens. Development of the National Immunization Calendar as well as challenges in preventive vaccination system both are significant investment into the future. Advantages of vaccination are not limited only by infection diseases control. Experts of World Health Organization recognize positive influence of immunization on economic. Vaccines give unprecedented opportunities on alleviation of human sufferings but it can be possible only due to perfect work of immunization calendar. It is necessary to estimate our National Immunization Calendar alongside with suggested by World Health Organization and professional associations plans. It is essential to estimate experience and facilities of modern vaccinology. This entailed the optimal preventive vaccination schedule, which can be implemented in the structure of existing national calendar.