Prospects For Development Of Vaccines Research Articles

Immunogenesis in Lassa fever and prospects for vaccine development

Analysis of literature data on the structure of the Lassa virus genome and its strain diversity has shown that the molecular heterogeneity of strains is essential in the design of vaccines and evaluation of their efficacy, which is determined by the relevant WHO recommendations. During virus reproduction, Lassa counteracts cellular immunogenesis by suppressing the expression of the suppressor of signaling proteins, cytokines and the RLR receptor that recognizes viral two-segmented RNA.
 The GP protein, which determines the pathogen's infectivity and tropism, should be the main target for vaccines being developed. Other targets are the processes of viral RNA synthesis that determine the features of immunogenesis. A study of the immunogenesis of Lassa fever shows that the preferred candidate would be a replicating apathogenic vaccine capable of inducing an optimal combination of cellular and humoral responses, that is, causing high activity of T-lymphocytes and the production of viral neutralizing antibodies. One of the most important characteristics of a live candidate vaccine should be genetic stability to exclude reversion to a more pathogenic genotype.
 Of the more than 130 candidate vaccines against Lassa fever designed, only two being the most promising were tested for immunogenicity and safety in humans (a recombinant on the measles virus platform and a DNA vaccine). A recombinant of Lassa virus with vesicular stomatitis virus and reassortants of Mopeya and Lassa viruses (MOPV/LASV- ML29) and (r3ML29) are promising for further development. A candidate vaccine rVSVG/LVGPC, similar in design to the rVSVG-ZEBOV-GP vaccine against Ebola, is promising.

Development of Fish Parasite Vaccines in the OMICs Era: Progress and Opportunities.

Globally, parasites are increasingly being recognized as catastrophic agents in both aquaculture sector and in the wild aquatic habitats leading to an estimated annual loss between 1.05 billion and 9.58 billion USD. The currently available therapeutic and control measures are accompanied by many limitations. Hence, vaccines are recommended as the “only green and effective solution” to address these concerns and protect fish from pathogens. However, vaccine development warrants a better understanding of host–parasite interaction and parasite biology. Currently, only one commercial parasite vaccine is available against the ectoparasite sea lice. Additionally, only a few trials have reported potential vaccine candidates against endoparasites. Transcriptome, genome, and proteomic data at present are available only for a limited number of aquatic parasites. Omics-based interventions can be significant in the identification of suitable vaccine candidates, finally leading to the development of multivalent vaccines for significant protection against parasitic infections in fish. The present review highlights the progress in the immunobiology of pathogenic parasites and the prospects of vaccine development. Finally, an approach for developing a multivalent vaccine for parasitic diseases is presented. Data sources to prepare this review included Pubmed, google scholar, official reports, and websites.

Advances and Prospects in Vaccine Development against Enterococci.

Enterococci are the second most common Gram-positive pathogen responsible for nosocomial infections. Due to the limited number of new antibiotics that reach the medical practice and the resistance of enterococci to the current antibiotic options, passive and active immunotherapies have emerged as a potential prevention and/or treatment strategy against this opportunistic pathogen. In this review, we explore the pathogenicity of these bacteria and their interaction with the host immune response. We provide an overview of the capsular polysaccharides and surface-associated proteins that have been described as potential antigens in anti-enterococcal vaccine formulations. In addition, we describe the current status in vaccine development against enterococci and address the importance and the current advances toward the development of well-defined vaccines with broad coverage against enterococci.

‘PANDEMIC DIPLOMACY’ AND THE POLITICS OF PARADOX: INTERNATIONAL COOPERATION IN THE AGE OF NATIONAL DISTANCING

Since the end of the Cold War no development has unravelled the international political system as much as COVID-19 pandemic. A health crisis is reshaping international politics, undermining global economy, frustrating global climate change talks, and creating several new challenges for diplomacy. Paradoxically, the world is coming together to combat a disease in a time of international travel bans, border closures and national distancing. In another dimension, nationalism is trumping internationalism in a time of global pandemic, where international cooperation offers hope. While the pandemic heralds a new order of international politics and diplomacy given its many legacies and challenges, it sustains the old order of super power rivalry, competition and cooperation. As COVID-19 pandemic untangles, political and diplomatic contradictions reinforce inter-state relations and create uncertainties around the prospects of vaccine development and the nature of post-COVID-19 world order. This study seeks to interrogate diplomatic practices of COVID-19 and how they have shaped global politics and diplomacy since the outbreak of the pandemic. The study argues that COVID-19 is a diplomatic and political paradox, and the challenges created by the pandemic have come to stay and will form the building blocks of global politics and diplomacy in the post pandemic era. Renewed inter-state relations and collaborations will provide a pathway to global prosperity post-COVID-19.

Challenges and prospects of COVID-19 vaccine development based on the progress made in SARS and MERS vaccine development.

The outbreak of coronavirus disease 2019 (COVID‐19) as a pandemic has shaken the global health system and economy by their roots. This epidemic is still spreading and showing no signs of decreasing trend. Vaccination could be the only effective and economical means to control this pandemic. A number of research institutions and pharmaceutical companies have plunged into the race of vaccine development against COVID‐19 which are in various stages of development. An intriguing fact of coronavirus infections is that in every decade of the 21st century there is a new major coronavirus epidemic, namely, severe acute respiratory syndrome (SARS) in 2002, Middle East respiratory syndrome (MERS) in 2012, and now COVID‐19; and such epidemics are expected in future too. Since most of the biological characteristics of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) are still obscure, the scientists are relying on the information available on SARS‐CoV and to some extent on MERS‐CoV for designing and developing COVID‐19 vaccines. But there is a need of vigorous testing for immunogenicity, safety, efficacy, and level of protection conferred in the hosts. This review focuses on the challenges and prospects of vaccine development against COVID‐19. It highlights seriousness, bottlenecks in vaccine development, possible vaccine candidates, different vaccine strategies, safety evaluation issues, and vaccine production processes pertaining to COVID‐19 based on the knowledge acquired on SARS and MERS vaccine development in the past.

Cholera: Immunity and Prospects in Vaccine Development.

Vibrio cholerae is a prototypical noninvasive mucosal pathogen, yet infection generates long-lasting protection against subsequent disease. Vibriocidal antibody responses are an imperfect but established correlate of protection against cholera following both infection and vaccination. However, vibriocidal antibody responses are likely a surrogate marker for longer-lasting functional immune responses that target the O-polysaccharide antigen at the mucosal surface. While the current bivalent inactivated oral whole cell vaccine is being increasingly used to prevent cholera in areas where the disease is a threat, the most significant limitation of this vaccine is it offers relatively limited direct protection in young children. Future strategies for cholera vaccination include the development of cholera conjugate vaccines and the further development of live attenuated vaccines. Ultimately, the goal of a multivalent vaccine for cholera and other childhood enteric infections that can be incorporated into a standard immunization schedule should be realized.

Development of Novel Vaccines Against Infectious Diseases Based on Chimpanzee Adenoviral Vector.

Vaccination is considered to be the most effective method of preventing infectious or other diseases. Adenovirus (Ad) is one the most promising vectors in vaccine research and development. It can induce not only potent humoral but also cellular immune responses, and has therefore been widely applied in basic and translational studies. Chimpanzee Ad is a rare serotype circulating in humans. This circumvents the problem of preexisting immunity to human Ad serotypes, enhancing Chimpanzee Ad prospects in vaccine development. Here we describe experimental procedures used to generate a new generation of rabies vaccine based on a chimpanzee Ad vector, which can be extended in the development of novel vaccines against other infectious diseases.

Chlamydia trachomatis: Protective Adaptive Responses and Prospects for a Vaccine.

Chlamydia trachomatis is the most common cause of sexually transmitted bacterial infection globally. These infections translate to a significant public health burden, particularly women's healthcare costs due to serious disease sequelae such as pelvic inflammatory disease (PID), tubal factor infertility, chronic pelvic pain, and ectopic pregnancy. There is no evidence that natural immunity can provide complete, long-term protection necessary to prevent chronic pathology, making human vaccine development critical. Vaccine design will require careful consideration of protective versus pathological host-response mechanisms in concert with elucidation of optimal antigens and adjuvants. Evidence suggests that a Th1 response, facilitated by IFN-γ-producing CD4 T cells, will be instrumental in generating long-term, sterilizing immunity. Although the role of antibodies is not completely understood, they have exhibited a protective effect by enhancing chlamydial clearance. Future work will require investigation of broadly neutralizing antibodies and antibody-augmented cellular immunity to successfully design a vaccine that potently elicits both arms of the immune response. Sterilizing immunity is the ultimate goal. However, vaccine-induced partial immunity that prevents upper genital tract infection and inflammation would be cost-effective compared to current screening and treatment strategies. In this chapter, we examine evidence from animal and human studies demonstrating protective adaptive immune responses to Chlamydia and discuss future challenges and prospects for vaccine development.

Antigens of Corynebacterium pseudotuberculosis and prospects for vaccine development

Corynebacterium pseudotuberculosis continues to cause considerable economic losses in ovine and caprine herds worldwide, causing caseous lymphadenitis. Nevertheless, the immunology of this disease is relatively unknown. Novel antigens may provide vaccines that are more effective and improve diagnostic methods for better control of this disease. The available commercial vaccines are not able to fully protect susceptible animals, cannot be used in all host species and are not licensed for use in many countries. Recent studies on the genomics of C. pseudotuberculosis and on its molecular determinants of virulence should bring us new alternatives for more effective vaccine formulations.

Mapping and analysis of West Nile virus-specific monoclonal antibodies: prospects for vaccine development

Seasonal epidemics of West Nile virus (WNV) infection now occur throughout North America, causing clinical symptoms ranging from fever to encephalitis. There are no specific treatment options or licensed vaccines. Several classically developed vaccine candidates are being evaluated in clinical trials. However, questions of safety and/or immunogenicity may limit their usefulness. Mapping of human and murine antibody repertoires against the WNV envelope protein after WNV infection have revealed important insights into the protective immune response against the virus. This review will give an overview of vaccines under development and summarize current data on E-protein antigenicity that could aid in the design of next generation WNV vaccines.

Prospects for development of vaccines against fungal diseases

Despite recent additions to our antifungal drug armamentarium, success rates for many mycoses remain unacceptably low and antifungal drug therapy is often limited by toxicity, resistance and high cost. To circumvent these difficulties, alternative approaches to prevention and treatment are being developed, including vaccines and passive immunotherapy. Here, we review the progress of current research in this field, discuss some of the potential obstacles to developing and marketing a protective antifungal vaccine, and summarize two clinical trials of monoclonal antibodies as adjunctive treatment of established mycoses. In animal models of fungal infections, protective responses have been elicited with vaccines composed of whole organisms, soluble cell free fractions, purified proteins, glycans and nucleic acids. Methods to boost the immune response to vaccination include the use of adjuvants and antigen-loaded dendritic cells (DCs). A significant challenge to the development of effective vaccines will be to elicit immune responses in immunocompromised individuals who are most at risk for invasive fungal infections.

Extraintestinal isolates of Escherichia coli : identification and prospects for vaccine development

Extraintestinal pathogenic Escherichia coli (ExPEC) cause a wide variety of infections that are responsible for significant morbidity, mortality and costs to our healthcare system. Thereby, the development of an efficacious ExPEC vaccine will minimize disease and may be cost-effective in selected patient groups. Surface polysaccharides, such as capsule, have been traditional targets for vaccine development. Considering that significant antigenic heterogeneity exists among surface polysaccharides present in various ExPEC strains, their use as vaccine candidates will be challenging. Therefore, alternative vaccine candidates/approaches are being identified and evaluated and are discussed in this review. The authors envision that an efficacious ExPEC vaccine will consist of either a polyvalent subunit vaccine or a genetically engineered killed whole-cell vaccine.

Sheep-associated malignant catarrhal fever virus: prospects for vaccine development

Sheep-associated malignant catarrhal fever is emerging as a significant problem for several ruminant species worldwide. The inability to propagate the causative agent, ovine herpesvirus 2, in vitro has seriously hindered research efforts in the development of effective programs for control of the disease in clinically susceptible hosts. Recent molecular technologic advances have provided powerful tools for investigating this difficult-to-study virus. Identification of the infectious virus source, establishment of experimental animal models and completion of sequencing the genome for ovine herpesvirus 2 have put us in a position to pursue the development of vaccines for control of the disease. In this review, the authors briefly describe the current understanding of ovine herpesvirus 2 and prospectively discuss vaccine development against the virus.

Ricin: current understanding and prospects for an antiricin vaccine

Ricin is a potent cytotoxin that can be rapidly internalized into mammalian cells leading to cell death. The ease in obtaining the toxin and its deadly nature combine to implicate ricin as a convenient agent for bioterrorism. Research into the mechanism of toxicity, as well as strategies for treatment and protection from the toxin has been widely undertaken for a number of years. This article reviews the current understanding of the mechanism of action of the toxin, the clinical effects of ricin intoxication and how these relate to current and continuing prospects for vaccine development.

Chlamydia trachomatis infection: incidence, health costs and prospects for vaccine development

Chlamydia trachomatis infection is now the most common sexually transmitted disease worldwide. World Health Organisation figures estimated that 89 million new cases of genital Chlamydia infections occurred in 1995, highlighting the worldwide prevalence of infections and the economic burden on healthcare delivery. A number of methods have been developed for detection of chlamydial infection, which vary in sensitivity and specificity. No single method has yet gained general acceptance and in many countries Chlamydia infections are not reported, suggesting that the above figures may be an underestimate of the problem. As yet there is no consensus as to what constitutes a protective immune response against genital Chlamydia infection. Studies in animal models have shown that cell-mediated immunity, both Th1-driven macrophage activation and cytotoxic T cell responses, as well as antibody can mediate protection at different stages of the chlamydial life cycle. A successful vaccine would probably need to elicit both a systemic cell-mediated immune response to limit/resolve established infections and a mucosal IgA response to reduce bacterial shedding and the resulting spread of infection to partners of infected individuals. The immune response to Chlamydia, either through natural infection or following immunisation, also has the potential to enhance inflammation and to act as a driving force for constant mutation in the variable regions of the major outer membrane protein. As a result a constant prevalence of infection is maintained even in an immune population through the emergence of new allelic variants. Immune responses against antigens such as the 60 kDa heat shock protein can exacerbate inflammation through molecular mimicry and must not be elicited as a result of vaccination. Thus there are many challenges for the development of a successful vaccine which must elicit immunity against multiple serovars while at the same time minimising damaging pro-inflammatory immune responses.

TAP peptide transporter-independent presentation of heat-killed Sendai virus antigen on MHC class I molecules by splenic antigen-presenting cells.

Immunization of C57BL/6 (B6) mice with heat-killed Sendai virus generates a Sendai virus-specific CD8+ T cell response. This suggests that APC have the capacity to take up and present exogenous (nonreplicative) Sendai virus Ag on MHC class I molecules. Little is known about the intracellular requirements for processing of this form of Ag and its presentation on MHC class I. Therefore, we have studied the processing and presentation of heat-killed Sendai virus Ag on MHC class I molecules in splenic APC. Heat-killed Sendai virus Ags were efficiently processed by normal B6 as well as by TAP-1(-/-) splenic APC. Presentation was MHC class I restricted, since no presentation was seen by APC from TAP-1/beta2m-/- mice that lack expression of MHC class I. Presentation occurred even in the presence of brefeldin A, but was blocked by cytochalasin D as well as chloroquine. Finally, B6 as well as TAP-1(-/-) splenic APC, loaded with heat-killed Sendai virus Ag in vitro, primed naive CD8+ T cells in vivo. These studies suggest the existence of a TAP-independent pathway for Ag presentation on MHC class I in normal splenic APC, bearing many similarities with the MHC class II pathway for Ag presentation. The present results are discussed in relation to the events underlying the processing and presentation of exogenous Ag on MHC class I, the molecular basis for CD8+ T cell priming during viral infections, and prospects for vaccine development.

Erratum

In the December 1996 issue of JID, there is an error in the first column of table 2 of the Perspective (McCarthy JS, Nutman TR. Perspective: prospects for development of vaccines against human helminth infections. J Infect Dis 1996; 174: 1384–90). The word “cestode” should be “trematode.” The table with the correction is shown below.

Perspective: prospects for development of vaccines against human helminth infections.

The global prevalence of infection with parasitic worms or helminths likely exceeds that of any other infection. One-third of the world's population is estimated to harbor infection with intestinal helminths (Trichuris trichuria, Ascaris lumbricoides, Strongyloides stercoralis, or hookworm) [1]; between 200 and 300 million people are believed to be infected with one of the three species of schistosomes (Schistosoma mansoni, Schistosoma haematobium, Schistosoma japonicum) [2], and> 150 million are infected with one of the pathogenic :filarial parasites (Wuchereria bancrofti, Brugia malayi, Onchocerca volvulus, Loa loa) [3, 4]. The burden of helminth infection rests largely on the population of the developing world, where many persons carry infection with more than one of these parasites [5]. While nematode infection uncommonly leads to severe acute illness or death, a growing body of evidence indicates that chronic infection leads to patterns of morbidity and economic hardship not generally appreciated. For example, while heavy and chronic hookworm infection is a well-rccogmced cause of anemia, recent intervention studies have revealed that one course of anthelmintic treatment of schoolchildren leads to a sustained improvement in growth [6] and in academic performance [7]. Blinding eye disease is responsible for only part of the adverse impact of onchocerciasis, with chronic skin disease leading to major reduction in quality of life and economic productivity [4]. Helminth infection differs in a number of important ways from most other infectious diseases differences that have a major impact on possible strategies for disease control. First, with few exceptions, helminths do not multiply within the human host but require passage through the environment and an arthropod vector or other invertebrate host (such as a snail) to reproduce and complete the life cycle. This offers the possibility of vector control or other environmental measures as means of disease control. Second, helminth infection may persist for years, an important consideration when control by chemotherapy or vector control is contemplated. For example, it is necessary to maintain onchocerciasis control programs using ivermectin (which is inactive against the adult worm) and vector control for 10-15 years (the life span of the adult worm). Third, the clinical effects of infection are not directly related

Staphylococcal vaccines: a realistic dream.

Staphylococcus aureus, especially multidrug resistant strains, continues to be a leading cause of serious nosocomial infections. In spite of the debate among investigators in the field, the discovery of serologically distinct capsular polysaccharides on the surface of clinical isolates has renewed the prospects for development of vaccines and passive protective immunity against S. aureus infections. Capsular polysaccharide conjugate vaccines have now been produced and proven to be safe and immunogenic in both healthy and in a significant percentage of immunocompromised patients. Antibodies generated in humans against these vaccines have been shown to mediate type-specific opsonophagocytosis, and to protect animals against lethal challenge with the appropriate S. aureus isolate.

Vaccination against Lucilia cuprina: The causative agent of sheep blowfly strike

The sheep blowfly, Lucilia cuprina, is responsible for over 80% of cases of blowfly strike in Australia and the losses in production and sheep deaths due to flystrike exceed $200 million per annum. Traditional methods of control are becoming less effective because of the blowfly's resistance to insecticides and thus other methods of control are necessary. In general, sheep develop very little immunity to flystrike even after repeated infestation, however vaccination against L. cuprina has shown considerable potential for controlling flystrike. The most successful sources of antigens have been the larvae's secreted proteases and several extracts from gut or peritrophic membrane. Immunization with these antigens results in retardation of larval growth and in some cases larval mortality. On sheep immunized with peritrophic membrane extracts, the growth retardation appears to be caused by a blocking of the peritrophic membrane which results in the larvae being starved of nutrients. The prospects for vaccine development and the remaining barriers to be overcome are discussed.