scholarly journals Vaccines against malaria

2011 ◽  
Vol 366 (1579) ◽  
pp. 2806-2814 ◽  
Author(s):  
Adrian V. S. Hill
Keyword(s):  
Life Cycle ◽  
Malaria Vaccine ◽  
Vaccine Development ◽  
Viral Vector ◽  
Cost Effective ◽  
Life Cycle Stage ◽  
Phase Iii ◽  
Small Scale ◽  
Vaccine Candidates ◽  
Adjuvant Vaccine

There is no licenced vaccine against any human parasitic disease and Plasmodium falciparum malaria, a major cause of infectious mortality, presents a great challenge to vaccine developers. This has led to the assessment of a wide variety of approaches to malaria vaccine design and development, assisted by the availability of a safe challenge model for small-scale efficacy testing of vaccine candidates. Malaria vaccine development has been at the forefront of assessing many new vaccine technologies including novel adjuvants, vectored prime-boost regimes and the concept of community vaccination to block malaria transmission. Most current vaccine candidates target a single stage of the parasite's life cycle and vaccines against the early pre-erythrocytic stages have shown most success. A protein in adjuvant vaccine, working through antibodies against sporozoites, and viral vector vaccines targeting the intracellular liver-stage parasite with cellular immunity show partial efficacy in humans, and the anti-sporozoite vaccine is currently in phase III trials. However, a more effective malaria vaccine suitable for widespread cost-effective deployment is likely to require a multi-component vaccine targeting more than one life cycle stage. The most attractive near-term approach to develop such a product is to combine existing partially effective pre-erythrocytic vaccine candidates.

scholarly journals In silico characterisation of putative Plasmodium falciparum vaccine candidates in African malaria populations

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
O. Ajibola ◽  
M. F. Diop ◽  
A. Ghansah ◽  
L. Amenga-Etego ◽  
L. Golassa ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Vaccine ◽  
Transmembrane Domain ◽  
Vaccine Development ◽  
Balancing Selection ◽  
Immune Recognition ◽  
African Countries ◽  
Vaccine Candidates ◽  
D Values ◽  
Tajima’S D

AbstractGenetic diversity of surface exposed and stage specific Plasmodium falciparum immunogenic proteins pose a major roadblock to developing an effective malaria vaccine with broad and long-lasting immunity. We conducted a prospective genetic analysis of candidate antigens (msp1, ama1, rh5, eba175, glurp, celtos, csp, lsa3, Pfsea, trap, conserved chrom3, hyp9, hyp10, phistb, surfin8.2, and surfin14.1) for malaria vaccine development on 2375 P. falciparum sequences from 16 African countries. We described signatures of balancing selection inferred from positive values of Tajima’s D for all antigens across all populations except for glurp. This could be as a result of immune selection on these antigens as positive Tajima’s D values mapped to regions with putative immune epitopes. A less diverse phistb antigen was characterised with a transmembrane domain, glycophosphatidyl anchors between the N and C- terminals, and surface epitopes that could be targets of immune recognition. This study demonstrates the value of population genetic and immunoinformatic analysis for identifying and characterising new putative vaccine candidates towards improving strain transcending immunity, and vaccine efficacy across all endemic populations.

scholarly journals Characterization of the Immune Response of MERS-CoV Vaccine Candidates Derived from Two Different Vectors in Mice

Viruses ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 125 ◽  
Author(s):  
Entao Li ◽  
Feihu Yan ◽  
Pei Huang ◽  
Hang Chi ◽  
Shengnan Xu ◽  
...  
Keyword(s):  
Immune Responses ◽  
Antibody Response ◽  
Rabies Virus ◽  
Vaccine Development ◽  
Vaccine Candidate ◽  
Viral Vector ◽  
Vaccine Vector ◽  
Vaccine Candidates ◽  
Cellular Immune Responses ◽  
Cellular Immune

Middle East respiratory syndrome (MERS) is an acute, high-mortality-rate, severe infectious disease caused by an emerging MERS coronavirus (MERS-CoV) that causes severe respiratory diseases. The continuous spread and great pandemic potential of MERS-CoV make it necessarily important to develop effective vaccines. We previously demonstrated that the application of Gram-positive enhancer matrix (GEM) particles as a bacterial vector displaying the MERS-CoV receptor-binding domain (RBD) is a very promising MERS vaccine candidate that is capable of producing potential neutralization antibodies. We have also used the rabies virus (RV) as a viral vector to design a recombinant vaccine by expressing the MERS-CoV S1 (spike) protein on the surface of the RV. In this study, we compared the immunological efficacy of the vaccine candidates in BALB/c mice in terms of the levels of humoral and cellular immune responses. The results show that the rabies virus vector-based vaccine can induce remarkably earlier antibody response and higher levels of cellular immunity than the GEM particles vector. However, the GEM particles vector-based vaccine candidate can induce remarkably higher antibody response, even at a very low dose of 1 µg. These results indicate that vaccines constructed using different vaccine vector platforms for the same pathogen have different rates and trends in humoral and cellular immune responses in the same animal model. This discovery not only provides more alternative vaccine development platforms for MERS-CoV vaccine development, but also provides a theoretical basis for our future selection of vaccine vector platforms for other specific pathogens.

scholarly journals Advances and challenges in malaria vaccine development

2009 ◽  
Vol 11 ◽  
Author(s):  
Ruobing Wang ◽  
Joseph D. Smith ◽  
Stefan H.I. Kappe
Keyword(s):  
Life Cycle ◽  
Subunit Vaccine ◽  
Malaria Vaccine ◽  
Vaccine Development ◽  
Control Strategies ◽  
Complex Life Cycle ◽  
Mosquito Vector ◽  
Specific Stage ◽  
Specific Species ◽  
Induced Immunity

Malaria remains one of the most devastating infectious diseases that threaten humankind. Human malaria is caused by five different species ofPlasmodiumparasites, each transmitted by the bite of femaleAnophelesmosquitoes. Plasmodia are eukaryotic protozoans with more than 5000 genes and a complex life cycle that takes place in the mosquito vector and the human host. The life cycle can be divided into pre-erythrocytic stages, erythrocytic stages and mosquito stages. Malaria vaccine research and development faces formidable obstacles because many vaccine candidates will probably only be effective in a specific species at a specific stage. In addition,Plasmodiumactively subverts and escapes immune responses, possibly foiling vaccine-induced immunity. Although early successful vaccinations with irradiated, live-attenuated malaria parasites suggested that a vaccine is possible, until recently, most efforts have focused on subunit vaccine approaches. Blood-stage vaccines remain a primary research focus, but real progress is evident in the development of a partially efficacious recombinant pre-erythrocytic subunit vaccine and a live-attenuated sporozoite vaccine. It is unlikely that partially effective vaccines will eliminate malaria; however, they might prove useful in combination with existing control strategies. Elimination of malaria will probably ultimately depend on the development of highly effective vaccines.

scholarly journals Antibody Targets and Properties for Complement-Fixation Against the Circumsporozoite Protein in Malaria Immunity

2021 ◽  
Vol 12 ◽  
Author(s):  
Liriye Kurtovic ◽  
Damien R. Drew ◽  
Arlene E. Dent ◽  
James W. Kazura ◽  
James G. Beeson
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Vaccine ◽  
Vaccine Development ◽  
Complement Fixation ◽  
Terminal Region ◽  
Antibody Responses ◽  
Circumsporozoite Protein ◽  
Full Length ◽  
Acquired Immunity ◽  
Vaccine Candidates

The Plasmodium falciparum circumsporozoite protein (CSP) forms the basis of leading subunit malaria vaccine candidates. However, the mechanisms and specific targets of immunity are poorly defined. Recent findings suggest that antibody-mediated complement-fixation and activation play an important role in immunity. Here, we investigated the regions of CSP targeted by functional complement-fixing antibodies and the antibody properties associated with this activity. We quantified IgG, IgM, and functional complement-fixing antibody responses to different regions of CSP among Kenyan adults naturally exposed to malaria (n=102) and using a series of rabbit vaccination studies. Individuals who acquired functional complement-fixing antibodies had higher IgG, IgM and IgG1 and IgG3 to CSP. Acquired complement-fixing antibodies targeted the N-terminal, central-repeat, and C-terminal regions of CSP, and positive responders had greater antibody breadth compared to those who were negative for complement-fixing antibodies (p<0.05). Using rabbit vaccinations as a model, we confirmed that IgG specific to the central-repeat and non-repeat regions of CSP could effectively fix complement. However, vaccination with near full length CSP in rabbits poorly induced antibodies to the N-terminal region compared to naturally-acquired immunity in humans. Poor induction of N-terminal antibodies was also observed in a vaccination study performed in mice. IgG and IgM to all three regions of CSP play a role in mediating complement-fixation, which has important implications for malaria vaccine development.

scholarly journals Developmental Landscape of Potential Vaccine Candidates Based on Viral Vector for Prophylaxis of COVID-19

2021 ◽  
Vol 8 ◽  
Author(s):  
Rajashri Bezbaruah ◽  
Pobitra Borah ◽  
Bibhuti Bhushan Kakoti ◽  
Nizar A. Al-Shar’I ◽  
Balakumar Chandrasekaran ◽  
...  
Keyword(s):  
Viral Vectors ◽  
Ebola Virus ◽  
Vaccine Development ◽  
Viral Vector ◽  
World Health ◽  
Prolonged Incubation ◽  
Vaccine Candidates ◽  
Vector Vaccine ◽  
Dna And Rna ◽  
Viral Vector Vaccine

Severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, arose at the end of 2019 as a zoonotic virus, which is the causative agent of the novel coronavirus outbreak COVID-19. Without any clear indications of abatement, the disease has become a major healthcare threat across the globe, owing to prolonged incubation period, high prevalence, and absence of existing drugs or vaccines. Development of COVID-19 vaccine is being considered as the most efficient strategy to curtail the ongoing pandemic. Following publication of genetic sequence of SARS-CoV-2, globally extensive research and development work has been in progress to develop a vaccine against the disease. The use of genetic engineering, recombinant technologies, and other computational tools has led to the expansion of several promising vaccine candidates. The range of technology platforms being evaluated, including virus-like particles, peptides, nucleic acid (DNA and RNA), recombinant proteins, inactivated virus, live attenuated viruses, and viral vectors (replicating and non-replicating) approaches, are striking features of the vaccine development strategies. Viral vectors, the next-generation vaccine platforms, provide a convenient method for delivering vaccine antigens into the host cell to induce antigenic proteins which can be tailored to arouse an assortment of immune responses, as evident from the success of smallpox vaccine and Ervebo vaccine against Ebola virus. As per the World Health Organization, till January 22, 2021, 14 viral vector vaccine candidates are under clinical development including 10 nonreplicating and four replicating types. Moreover, another 39 candidates based on viral vector platform are under preclinical evaluation. This review will outline the current developmental landscape and discuss issues that remain critical to the success or failure of viral vector vaccine candidates against COVID-19.

scholarly journals Malaria vaccine candidates displayed on novel virus-like particles are immunogenic and induce transmission-blocking activity

2019 ◽  
Author(s):  
Jo-Anne Chan ◽  
David Wetzel ◽  
Linda Reiling ◽  
Kazutoyo Miura ◽  
Damien Drew ◽  
...  
Keyword(s):  
Malaria Vaccine ◽  
Vaccine Development ◽  
Transmission Blocking ◽  
Vaccine Candidates ◽  
Virus Like Particles ◽  
Malaria Vaccines ◽  
Membrane Feeding ◽  
B Virus ◽  
Vaccine Antigens ◽  
Novel Virus

ABSTRACTThe development of effective malaria vaccines remains a global health priority. Currently, the most advanced vaccine, known as RTS,S, has only shown modest efficacy in clinical trials. Thus, the development of more efficacious vaccines by improving the formulation of RTS,S for increased efficacy or to interrupt malaria transmission are urgently needed. The RTS,S vaccine is based on the presentation of a fragment of the sporozoite antigen on the surface of virus-like particles (VLPs) based on human hepatitis B virus (HBV). In this study, we have developed and evaluated a novel VLP platform based on duck HBV (known as Metavax) for malaria vaccine development. This platform can incorporate large and complex proteins into VLPs and is produced in a Hansenula cell line compatible with cGMP vaccine production. Here, we have established the expression of leading P. falciparum malaria vaccine candidates as VLPs. This includes Pfs230 and Pfs25, which are candidate transmission-blocking vaccine antigens. We demonstrated that the VLPs effectively induce antibodies to malaria vaccine candidates with minimal induction of antibodies to the duck-HBV scaffold antigen. Antibodies to Pfs230 also recognised native protein on the surface of gametocytes, and antibodies to both Pfs230 and Pfs25 demonstrated transmission-reducing activity in standard membrane feeding assays. These results establish the potential utility of this VLP platform for malaria vaccines, which may be suitable for the development of multi-component vaccines that achieve high vaccine efficacy and transmission-blocking immunity.

scholarly journals Vaccine Development for Severe Fever with Thrombocytopenia Syndrome

Viruses ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 627
Author(s):  
Tomoki Yoshikawa
Keyword(s):  
Animal Models ◽  
Vaccine Development ◽  
Viral Vector ◽  
Case Fatality ◽  
Small Animal ◽  
Primate Model ◽  
Hamster Model ◽  
Vaccine Candidates ◽  
Cat Model ◽  
Severe Fever

Severe fever with thrombocytopenia syndrome (SFTS), which is caused by SFTS virus (SFTSV), is a tick-borne emerging zoonosis with a high case-fatality rate. At present, there is no approved SFTS vaccine, although the development of a vaccine would be one of the best strategies for preventing SFTS. This article focused on studies aimed at establishing small animal models of SFTS that are indispensable for evaluating vaccine candidates, developing these vaccine candidates, and establishing more practical animal models for evaluation. Innate immune-deficient mouse models, a hamster model, an immunocompetent ferret model and a cat model have been developed for SFTS. Several vaccine candidates for SFTS have been developed, and their efficacy has been confirmed using these animal models. The candidates consist of live-attenuated virus-based, viral vector-based, or DNA-based vaccines. SFTS vaccines are expected to be used for humans and companion dogs and cats. Hence for practical use, the vaccine candidates should be evaluated for efficacy using not only nonhuman primates but also dogs and cats. There is no practical nonhuman primate model of SFTS; however, the cat model is available to evaluate the efficacy of these candidate SFTS vaccines on domesticated animals.

scholarly journals Modified Vaccinia Virus Ankara as a Viral Vector for Vaccine Candidates against Chikungunya Virus

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1122
Author(s):  
Juan García-Arriaza ◽  
Mariano Esteban ◽  
Daniel López
Keyword(s):  
Vaccinia Virus ◽  
Chikungunya Virus ◽  
Vaccine Development ◽  
Viral Vector ◽  
Severe Disease ◽  
Febrile Illness ◽  
Structural Proteins ◽  
Effective Vaccine ◽  
Vaccine Candidates ◽  
Modified Vaccinia Virus Ankara

There is a need to develop a highly effective vaccine against the emerging chikungunya virus (CHIKV), a mosquito-borne Alphavirus that causes severe disease in humans consisting of acute febrile illness, followed by chronic debilitating polyarthralgia and polyarthritis. In this review, we provide a brief history of the development of the first poxvirus vaccines that led to smallpox eradication and its implications for further vaccine development. As an example, we summarize the development of vaccine candidates based on the modified vaccinia virus Ankara (MVA) vector expressing different CHIKV structural proteins, paying special attention to MVA-CHIKV expressing all of the CHIKV structural proteins: C, E3, E2, 6K and E1. We review the characterization of innate and adaptive immune responses induced in mice and nonhuman primates by the MVA-CHIKV vaccine candidate and examine its efficacy in animal models, with promising preclinical findings needed prior to the approval of human clinical trials.

scholarly journals Current Clinical Trials Protocols and the Global Effort for Immunization against SARS-CoV-2

Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 474 ◽  
Author(s):  
Gabriel N. A. Rego ◽  
Mariana P. Nucci ◽  
Arielly H. Alves ◽  
Fernando A. Oliveira ◽  
Luciana C. Marti ◽  
...  
Keyword(s):  
Clinical Trials ◽  
United Arab Emirates ◽  
Vaccine Development ◽  
Viral Vector ◽  
Phase Iii ◽  
Vector Method ◽  
Phase Iii Clinical Trials ◽  
The United Kingdom ◽  
Global Center ◽  
The Usa

Coronavirus disease 2019 (COVID-19) is the biggest health challenge of the 21st century, affecting millions of people globally. The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has ignited an unprecedented effort from the scientific community in the development of new vaccines on different platforms due to the absence of a broad and effective treatment for COVID-19 or prevention strategy for SARS-CoV-2 dissemination. Based on 50 current studies selected from the main clinical trial databases, this systematic review summarizes the global race for vaccine development against COVID-19. For each study, the main intervention characteristics, the design used, and the local or global center partnerships created are highlighted. Most vaccine developments have taken place in Asia, using a viral vector method. Two purified inactivated SARS-CoV-2 vaccine candidates, an mRNA-based vaccine mRNA1273, and the chimpanzee adenoviral vaccine ChAdOx1 are currently in phase III clinical trials in the respective countries Brazil, the United Arab Emirates, the USA, and the United Kingdom. These vaccines are being developed based on a quickly formed network of collaboration.

scholarly journals Malaria vaccines: high-throughput tools for antigens discovery with potential for their development

2013 ◽  
pp. 121-128
Author(s):  
Nora Céspedes ◽  
Andrés Vallejo ◽  
Myriam Arévalo-Herrera ◽  
Sócrates Herrera
Keyword(s):  
Malaria Vaccine ◽  
Vaccine Development ◽  
Plasmodium Species ◽  
Cost Effective ◽  
Control Measures ◽  
Anopheles Mosquitoes ◽  
Malaria Vaccines ◽  
Large Numbers ◽  
Immune Potential ◽  
Selection Of

Malaria is a disease induced by parasites of the Plasmodium genus, which are transmitted by Anopheles mosquitoes and represents a great socio-economic burden worldwide. Plasmodium vivax is the second species of malaria worldwide, but it is the most prevalent in Latin America and other regions of the planet. It is currently considered that vaccines represent a cost-effective strategy for controlling transmissible diseases and could complement other malaria control measures; however, the chemical and immunological complexity of the parasite has hindered development of effective vaccines. Recent availability of several genomes of Plasmodium species, as well as bioinformatics tools are allowing the selection of large numbers of proteins and analysis of their immune potential. Herein, we review recently developed strategies for discovery of novel antigens with potential for malaria vaccine development.

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