Special Issue "Vaccine Candidates against Tropical Diseases"

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Vaccines against (re)emerging and Tropical Infections Diseases".

Deadline for manuscript submissions: closed (15 July 2020).

Special Issue Editors

Dr. Waleed Hussein
E-Mail Website
Guest Editor
School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Brisbane, Australia
Interests: Peptide-based vaccines; peptide synthesis; synthesis of enzyme inhibitors; gene delivery; peptide conjugations; Drug design; Group A Streptococcus; Malaria; human papilloma virus; Mycobacterium tuberculosis
Dr. Mariusz Skwarczynski
E-Mail Website
Guest Editor
School Of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD 4072, Australia
Interests: nanotechnology; peptide chemistry; medicinal chemistry; vaccine
Special Issues and Collections in MDPI journals
Prof. Dr. Istvan Toth
E-Mail Website1 Website2
Guest Editor
School of Chemistry and Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia
Interests: drug delivery; antimicrobial agents; prodrug strategies; macromolecules; adjuvants
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

Tropical diseases include all diseases that occur in the tropics alone or predominantly. The term is often used in practice to refer to infectious diseases that flourish under hot humid conditions. These neglected diseases that affect a large number of populations are potentially preventable. Under conditions of deprivation, neglected tropical diseases exist and are concentrated almost exclusively in the developing world's poor communities. Due to the devastating effects of tropical diseases on the human population, they have been listed among the top diseases with high global morbidity and mortality.

Despite the great need for an effective cure, there are still no vaccines available on the market against many of these diseases. This special issue focuses on the demonstration of efforts and attempts toward the development of effective vaccine candidates against different types of tropical diseases such as malaria, hookworm infections, group A streptococcus, tick-prone diseases, dengue virus infection and other tropical diseases.

Dr. Waleed Hussein
Dr. Mariusz Skwarczynski
Prof. Istvan Toth
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Vaccines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • vaccine candidates
  • Group A Streptococcus
  • Malaria
  • Dengue virus
  • Hookworm infection
  • Tick-borne diseases

Published Papers (10 papers)

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Research

Jump to: Review

Article
Pullulan-Coated Iron Oxide Nanoparticles for Blood-Stage Malaria Vaccine Delivery
Vaccines 2020, 8(4), 651; https://doi.org/10.3390/vaccines8040651 - 03 Nov 2020
Viewed by 691
Abstract
Vaccines against blood-stage malaria often aim to induce antibodies to neutralize parasite entry into red blood cells, interferon gamma (IFNγ) produced by T helper 1 (Th1) CD4+ T cells or interleukin 4 (IL-4) produced by T helper 2 (Th2) cells to provide B [...] Read more.
Vaccines against blood-stage malaria often aim to induce antibodies to neutralize parasite entry into red blood cells, interferon gamma (IFNγ) produced by T helper 1 (Th1) CD4+ T cells or interleukin 4 (IL-4) produced by T helper 2 (Th2) cells to provide B cell help. One vaccine delivery method for suitable putative malaria protein antigens is the use of nanoparticles as vaccine carriers. It has been previously shown that antigen conjugated to inorganic nanoparticles in the viral-particle size range (~40–60 nm) can induce protective antibodies and T cells against malaria antigens in a rodent malaria challenge model. Herein, it is shown that biodegradable pullulan-coated iron oxide nanoparticles (pIONPs) can be synthesized in this same size range. The pIONPs are non-toxic and do not induce conventional pro-inflammatory cytokines in vitro and in vivo. We show that murine blood-stage antigen MSP4/5 from Plasmodium yoelii could be chemically conjugated to pIONPs and the use of these conjugates as immunogens led to the induction of both specific antibodies and IFNγ CD4+ T cells reactive to MSP4/5 in mice, comparable to responses to MSP4/5 mixed with classical adjuvants (e.g., CpG or Alum) that preferentially induce Th1 or Th2 cells individually. These results suggest that biodegradable pIONPs warrant further exploration as carriers for developing blood-stage malaria vaccines. Full article
(This article belongs to the Special Issue Vaccine Candidates against Tropical Diseases)
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Article
Enhancement of Tetravalent Immune Responses to Highly Conserved Epitopes of a Dengue Peptide Vaccine Conjugated to Polystyrene Nanoparticles
Vaccines 2020, 8(3), 417; https://doi.org/10.3390/vaccines8030417 - 25 Jul 2020
Cited by 2 | Viewed by 835
Abstract
Vaccination remains the major approach to the prevention of dengue. Since the only licensed live attenuated vaccine (LAV) lacked efficacy against all four serotypes, other vaccine platforms, such as synthetic peptide vaccines, should be explored. In this study, four multi-epitope peptides (P1–P4) were [...] Read more.
Vaccination remains the major approach to the prevention of dengue. Since the only licensed live attenuated vaccine (LAV) lacked efficacy against all four serotypes, other vaccine platforms, such as synthetic peptide vaccines, should be explored. In this study, four multi-epitope peptides (P1–P4) were designed by linking a universal T-helper epitope (PADRE or TpD) to the highly conserved CD8 T cell epitope and B cell epitope (B1 or B2) against all four DENV serotypes. The multi-epitope peptides were conjugated to polystyrene nanoparticles (PSNPs) and four nanovaccines (NP1–NP4) were constructed. Mice immunized with NP1–NP4 elicited significantly higher titers of IgG and neutralizing antibodies when compared to immunization with naked P1–P4. The immune responses in mice immunized with peptide vaccines were compared with nanovaccines using ELISA, ELISPOT, and a neutralization test based on FRNT50. Among the four conjugated peptide nanovaccines, NP3 comprising the TpD T-helper epitope linked to the highly conserved B1 epitope derived from the E protein was able to elicit significant levels of IFN-γ and neutralizing antibodies to all four dengue serotypes. NP3 is a promising tetravalent synthetic peptide vaccine, but the selection of a more effective CD8+ T cell epitope and adjuvants to further improve the immunogenicity is warranted. Full article
(This article belongs to the Special Issue Vaccine Candidates against Tropical Diseases)
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Article
Schistosoma haematobium Extracellular Vesicle Proteins Confer Protection in a Heterologous Model of Schistosomiasis
Vaccines 2020, 8(3), 416; https://doi.org/10.3390/vaccines8030416 - 24 Jul 2020
Cited by 8 | Viewed by 1079
Abstract
Helminth parasites release extracellular vesicles which interact with the surrounding host tissues, mediating host–parasite communication and other fundamental processes of parasitism. As such, vesicle proteins present attractive targets for the development of novel intervention strategies to control these parasites and the diseases they [...] Read more.
Helminth parasites release extracellular vesicles which interact with the surrounding host tissues, mediating host–parasite communication and other fundamental processes of parasitism. As such, vesicle proteins present attractive targets for the development of novel intervention strategies to control these parasites and the diseases they cause. Herein, we describe the first proteomic analysis by LC-MS/MS of two types of extracellular vesicles (exosome-like, 120 k pellet vesicles and microvesicle-like, 15 k pellet vesicles) from adult Schistosoma haematobium worms. A total of 57 and 330 proteins were identified in the 120 k pellet vesicles and larger 15 k pellet vesicles, respectively, and some of the most abundant molecules included homologues of known helminth vaccine and diagnostic candidates such as Sm-TSP2, Sm23, glutathione S-transferase, saponins and aminopeptidases. Tetraspanins were highly represented in the analysis and found in both vesicle types. Vaccination of mice with recombinant versions of three of these tetraspanins induced protection in a heterologous challenge (S. mansoni) model of infection, resulting in significant reductions (averaged across two independent trials) in liver (47%, 38% and 41%) and intestinal (47%, 45% and 41%) egg burdens. These findings offer insight into the mechanisms by which anti-tetraspanin antibodies confer protection and highlight the potential that extracellular vesicle surface proteins offer as anti-helminth vaccines. Full article
(This article belongs to the Special Issue Vaccine Candidates against Tropical Diseases)
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Communication
Generation of a Peptide Vaccine Candidate against Falciparum Placental Malaria Based on a Discontinuous Epitope
Vaccines 2020, 8(3), 392; https://doi.org/10.3390/vaccines8030392 - 18 Jul 2020
Cited by 1 | Viewed by 723
Abstract
In pregnant women, Plasmodium falciparum-infected red blood cells adhere to the placenta via the parasite protein VAR2CSA. Two vaccine candidates based on VAR2CSA are currently in clinical trials; however, these candidates failed to elicit strain-transcending antibody responses. We previously showed that a [...] Read more.
In pregnant women, Plasmodium falciparum-infected red blood cells adhere to the placenta via the parasite protein VAR2CSA. Two vaccine candidates based on VAR2CSA are currently in clinical trials; however, these candidates failed to elicit strain-transcending antibody responses. We previously showed that a cross-reactive monoclonal antibody (3D10) raised against the P. vivax antigen PvDBP targets epitopes in VAR2CSA. We now aim to design a peptide vaccine against VAR2CSA based on the epitope that generated 3D10. We mapped the epitope to subdomain 1 (SD1) of PvDBP and identified a peptide that contained the minimal sequence. However, this peptide did not elicit cross-reactive VAR2CSA antibodies in mice. When tested against a broader, overlapping peptide array spanning SD1, 3D10 in fact recognized a discontinuous epitope consisting of three segments of SD1. These findings presented the challenge to generate this larger structural epitope as a synthetic peptide since it is stabilized by two pairs of disulfide bonds. We overcame this using a synthetic scaffold to conformationally constrain the SD1 peptide and coupled it to keyhole limpet hemocyanin (KLH). The SD1-KLH conjugate elicited antibodies in mice that cross-reacted with VAR2CSA. This strategy successfully recapitulated a discontinuous epitope with a synthetic peptide and represents the first heterologous vaccine candidate against VAR2CSA. Full article
(This article belongs to the Special Issue Vaccine Candidates against Tropical Diseases)
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Article
Opsonic Activity of Conservative Versus Variable Regions of the Group A Streptococcus M Protein
Vaccines 2020, 8(2), 210; https://doi.org/10.3390/vaccines8020210 - 07 May 2020
Cited by 3 | Viewed by 1084
Abstract
Group A Streptococcus (GAS) and GAS-associated infections are a global challenge, with no licensed GAS vaccine on the market. The GAS M protein is a critical virulence factor in the fight against GAS infection, and it has been a primary target for GAS [...] Read more.
Group A Streptococcus (GAS) and GAS-associated infections are a global challenge, with no licensed GAS vaccine on the market. The GAS M protein is a critical virulence factor in the fight against GAS infection, and it has been a primary target for GAS vaccine development. Measuring functional opsonic antibodies against GAS is an important component in the clinical development path for effective vaccines. In this study, we compared the opsonic activity of two synthetic, self-adjuvanting subunit vaccines containing either the J8- or 88/30-epitope in Swiss outbred mice using intranasal administration. Following primary immunization and three boosts, sera were assessed for IgG activity using ELISA, and opsonization activity against seven randomly selected clinical isolates of GAS was measured. Vaccine constructs containing the conservative J8-epitope showed significant opsonic activity against six out of the seven GAS clinical isolates, while the vaccine containing the variable 88/30-epitope did not show any significant opsonic activity. Full article
(This article belongs to the Special Issue Vaccine Candidates against Tropical Diseases)
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Article
Protective Malaria Vaccine in Mice Based on the Plasmodium vivax Circumsporozoite Protein Fused with the Mumps Nucleocapsid Protein
Vaccines 2020, 8(2), 190; https://doi.org/10.3390/vaccines8020190 - 19 Apr 2020
Cited by 2 | Viewed by 1279
Abstract
Plasmodium vivax is the most common species of human malaria parasite found outside Africa, with high endemicity in Asia, Central and South America, and Oceania. Although Plasmodium falciparum causes the majority of deaths, P. vivax can lead to severe malaria and result in [...] Read more.
Plasmodium vivax is the most common species of human malaria parasite found outside Africa, with high endemicity in Asia, Central and South America, and Oceania. Although Plasmodium falciparum causes the majority of deaths, P. vivax can lead to severe malaria and result in significant morbidity and mortality. The development of a protective vaccine will be a major step toward malaria elimination. Recently, a formulation containing the three allelic variants of the P. vivax circumsporozoite protein (PvCSP—All epitopes) showed partial protection in mice after a challenge with the hybrid Plasmodium berghei (Pb) sporozoite, in which the PbCSP central repeats were replaced by the VK210 PvCSP repeats (Pb/Pv sporozoite). In the present study, the chimeric PvCSP allelic variants (VK210, VK247, and P. vivax-like) were fused with the mumps virus nucleocapsid protein in the absence (NLP-CSPR) or presence of the conserved C-terminal (CT) domain of PvCSP (NLP-CSPCT). To elicit stronger humoral and cellular responses, Pichia pastoris yeast was used to assemble them as nucleocapsid-like particles (NLPs). Mice were immunized with each recombinant protein adjuvanted with Poly (I:C) and presented a high frequency of antigen-specific antibody-secreting cells (ASCs) on days 5 and 30, respectively, in the spleen and bone marrow. Moreover, high IgG titers against all PvCSP variants were detected in the sera. Later, these immunized mice with NLP-CSPCT were challenged with Pb/Pv sporozoites. Sterile protection was observed in 30% of the challenged mice. Therefore, this vaccine formulation use has the potential to be a good candidate for the development of a universal vaccine against P. vivax malaria. Full article
(This article belongs to the Special Issue Vaccine Candidates against Tropical Diseases)
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Review

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Review
Recent Progress in the Development of Liver Fluke and Blood Fluke Vaccines
Vaccines 2020, 8(3), 553; https://doi.org/10.3390/vaccines8030553 - 22 Sep 2020
Cited by 8 | Viewed by 1176
Abstract
Liver flukes (Fasciola spp., Opisthorchis spp., Clonorchis sinensis) and blood flukes (Schistosoma spp.) are parasitic helminths causing neglected tropical diseases that result in substantial morbidity afflicting millions globally. Affecting the world’s poorest people, fasciolosis, opisthorchiasis, clonorchiasis and schistosomiasis cause severe [...] Read more.
Liver flukes (Fasciola spp., Opisthorchis spp., Clonorchis sinensis) and blood flukes (Schistosoma spp.) are parasitic helminths causing neglected tropical diseases that result in substantial morbidity afflicting millions globally. Affecting the world’s poorest people, fasciolosis, opisthorchiasis, clonorchiasis and schistosomiasis cause severe disability; hinder growth, productivity and cognitive development; and can end in death. Children are often disproportionately affected. F. hepatica and F. gigantica are also the most important trematode flukes parasitising ruminants and cause substantial economic losses annually. Mass drug administration (MDA) programs for the control of these liver and blood fluke infections are in place in a number of countries but treatment coverage is often low, re-infection rates are high and drug compliance and effectiveness can vary. Furthermore, the spectre of drug resistance is ever-present, so MDA is not effective or sustainable long term. Vaccination would provide an invaluable tool to achieve lasting control leading to elimination. This review summarises the status currently of vaccine development, identifies some of the major scientific targets for progression and briefly discusses future innovations that may provide effective protective immunity against these helminth parasites and the diseases they cause. Full article
(This article belongs to the Special Issue Vaccine Candidates against Tropical Diseases)
Review
Anti-Flavivirus Vaccines: Review of the Present Situation and Perspectives of Subunit Vaccines Produced in Escherichia coli
Vaccines 2020, 8(3), 492; https://doi.org/10.3390/vaccines8030492 - 31 Aug 2020
Cited by 2 | Viewed by 1029
Abstract
This article aims to review the present status of anti-flavivirus subunit vaccines, both those at the experimental stage and those already available for clinical use. Aspects regarding development of vaccines to Yellow Fever virus, (YFV), Dengue virus (DENV), West Nile virus (WNV), Zika [...] Read more.
This article aims to review the present status of anti-flavivirus subunit vaccines, both those at the experimental stage and those already available for clinical use. Aspects regarding development of vaccines to Yellow Fever virus, (YFV), Dengue virus (DENV), West Nile virus (WNV), Zika virus (ZIKV), and Japanese encephalitis virus (JEV) are highlighted, with particular emphasis on purified recombinant proteins generated in bacterial cells. Currently licensed anti-flavivirus vaccines are based on inactivated, attenuated, or virus-vector vaccines. However, technological advances in the generation of recombinant antigens with preserved structural and immunological determinants reveal new possibilities for the development of recombinant protein-based vaccine formulations for clinical testing. Furthermore, novel proposals for multi-epitope vaccines and the discovery of new adjuvants and delivery systems that enhance and/or modulate immune responses can pave the way for the development of successful subunit vaccines. Nonetheless, advances in this field require high investments that will probably not raise interest from private pharmaceutical companies and, therefore, will require support by international philanthropic organizations and governments of the countries more severely stricken by these viruses. Full article
(This article belongs to the Special Issue Vaccine Candidates against Tropical Diseases)
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Review
Cocktail Anti-Tick Vaccines: The Unforeseen Constraints and Approaches toward Enhanced Efficacies
Vaccines 2020, 8(3), 457; https://doi.org/10.3390/vaccines8030457 - 19 Aug 2020
Cited by 6 | Viewed by 1165
Abstract
Ticks are second to mosquitoes as vectors of disease. Ticks affect livestock industries in Asia, Africa and Australia at ~$1.13 billion USD per annum. For instance, 80% of the global cattle population is at risk of infestation by the Rhipicephalus microplus species-complex, which [...] Read more.
Ticks are second to mosquitoes as vectors of disease. Ticks affect livestock industries in Asia, Africa and Australia at ~$1.13 billion USD per annum. For instance, 80% of the global cattle population is at risk of infestation by the Rhipicephalus microplus species-complex, which in 2016 was estimated to cause $22–30 billion USD annual losses. Although the management of tick populations mainly relies on the application of acaricides, this raises concerns due to tick resistance and accumulation of chemical residues in milk, meat, and the environment. To counteract acaricide-resistant tick populations, immunological tick control is regarded among the most promising sustainable strategies. Indeed, immense efforts have been devoted toward identifying tick vaccine antigens. Until now, Bm86-based vaccines have been the most effective under field conditions, but they have shown mixed success worldwide. Currently, of the two Bm86 vaccines commercialized in the 1990s (GavacTM in Cuba and TickGARDPLUSTM in Australia), only GavacTM is available. There is thus growing consensus that combining antigens could broaden the protection range and enhance the efficacies of tick vaccines. Yet, the anticipated outcomes have not been achieved under field conditions. Therefore, this review demystifies the potential limitations and proposes ways of sustaining enhanced cocktail tick vaccine efficacy. Full article
(This article belongs to the Special Issue Vaccine Candidates against Tropical Diseases)
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Review
Progress in the Development of Subunit Vaccines against Malaria
Vaccines 2020, 8(3), 373; https://doi.org/10.3390/vaccines8030373 - 10 Jul 2020
Cited by 2 | Viewed by 1260
Abstract
Malaria is a life-threatening disease and one of the main causes of morbidity and mortality in the human population. The disease also results in a major socio-economic burden. The rapid spread of malaria epidemics in developing countries is exacerbated by the rise in [...] Read more.
Malaria is a life-threatening disease and one of the main causes of morbidity and mortality in the human population. The disease also results in a major socio-economic burden. The rapid spread of malaria epidemics in developing countries is exacerbated by the rise in drug-resistant parasites and insecticide-resistant mosquitoes. At present, malaria research is focused mainly on the development of drugs with increased therapeutic effects against Plasmodium parasites. However, a vaccine against the disease is preferable over treatment to achieve long-term control. Trials to develop a safe and effective immunization protocol for the control of malaria have been occurring for decades, and continue on today; still, no effective vaccines are available on the market. Recently, peptide-based vaccines have become an attractive alternative approach. These vaccines utilize short protein fragments to induce immune responses against malaria parasites. Peptide-based vaccines are safer than traditional vaccines, relatively inexpensive to produce, and can be composed of multiple T- and B-cell epitopes integrated into one antigenic formulation. Various combinations, based on antigen choice, peptide epitope modification and delivery mechanism, have resulted in numerous potential malaria vaccines candidates; these are presently being studied in both preclinical and clinical trials. This review describes the current landscape of peptide-based vaccines, and addresses obstacles and opportunities in the production of malaria vaccines. Full article
(This article belongs to the Special Issue Vaccine Candidates against Tropical Diseases)
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