scholarly journals Resistance to Ticks and the Path to Anti-Tick and Transmission Blocking Vaccines

Vaccines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 725
Author(s):  
Jolieke G. van Oosterwijk ◽  
Stephen K. Wikel

The medical and veterinary public health importance of ticks and tick-borne pathogens is increasing due to the expansion of the geographic ranges of both ticks and pathogens, increasing tick populations, growing incidence of tick-borne diseases, emerging tick transmitted pathogens, and continued challenges of achieving effective and sustained tick control. The past decades show an increasing interest in the immune-mediated control of tick infestations and pathogen transmission through the use of vaccines. Bovine tick resistance induced by repeated infestations was reported over a century ago. This review addresses the phenomena and immunological underpinning of resistance to tick infestation by livestock and laboratory animals; the scope of tick countermeasures to host immune defenses; and the impact of genomics, functional genomics, and proteomics on dissecting complex tick–host–pathogen interactions. From early studies utilizing tick tissue extracts to salivary gland derived molecules and components of physiologically important pathways in tick gut and other tissues, an increased understanding of these relationships, over time, impacted the evolution of anti-tick vaccine antigen selection. Novel antigens continue to emerge, including increased interest in the tick microbiome. Anti-tick and transmission blocking vaccines targeting pathogen reservoirs have the potential to disrupt enzootic cycles and reduce human, companion, domestic animal, and wildlife exposure to infected ticks.

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Nicole G. Bender ◽  
Prachi Khare ◽  
Juan Martinez ◽  
Rebecca E. Tweedell ◽  
Vincent O. Nyasembe ◽  
...  

AbstractMalaria transmission-blocking vaccines (TBVs) prevent the completion of the developmental lifecycle of malarial parasites within the mosquito vector, effectively blocking subsequent infections. The mosquito midgut protein Anopheline alanyl aminopeptidase N (AnAPN1) is the leading, mosquito-based TBV antigen. Structure-function studies identified two Class II epitopes that can induce potent transmission-blocking (T-B) antibodies, informing the design of the next-generation AnAPN1. Here, we functionally screened new immunogens and down-selected to the UF6b construct that has two glycine-linked copies of the T-B epitopes. We then established a process for manufacturing UF6b and evaluated in outbred female CD1 mice the immunogenicity of the preclinical product with the human-safe adjuvant Glucopyranosyl Lipid Adjuvant in a liposomal formulation with saponin QS21 (GLA-LSQ). UF6b:GLA-LSQ effectively immunofocused the humoral response to one of the key T-B epitopes resulting in potent T-B activity, underscoring UF6b as a prime TBV candidate to aid in malaria elimination and eradication efforts.


2004 ◽  
Vol 72 (1) ◽  
pp. 584-588 ◽  
Author(s):  
Cevayir Coban ◽  
Ken J. Ishii ◽  
Anthony W. Stowers ◽  
David B. Keister ◽  
Dennis M. Klinman ◽  
...  

ABSTRACT Antibodies directed against Pfs25, a protein present on the surface of zygotes and ookinetes of Plasmodium falciparum, completely block pathogen transmission. We evaluated the immunomodulatory effect of CpG oligodeoxynucleotides (ODN) on the immunogenicity of recombinant Pfs25 (rPfs25) formulated in alum (Al). Immunization of mice with rPfs25 plus CpG ODN improved both the antibody titer (a 30-fold-higher antibody response than that with rPfs25-Al alone) and avidity. Coadministration of CpG ODN dramatically enhanced the titer of immunoglobulin G2A (IgG2a) compared to the titer of the IgG1-dominant response caused by rPfs25-Al alone, and the sera from the CpG ODN-coadministered group completely blocked the transmission of P. falciparum parasites to mosquitoes, as determined by membrane feeding assays. However, transmission-blocking experiments revealed that blocking efficacy was dependent on high-titer antibody levels, independent of isotypes. These results suggest that CpG ODN can be used as an adjuvant to enhance the immunogenicity of rPfs25 as a malaria transmission-blocking vaccine.


2020 ◽  
Author(s):  
Nicole G. Bender ◽  
Prachi Khare ◽  
Juan Martinez ◽  
Rebecca E. Tweedell ◽  
Vincent O. Nyasembe ◽  
...  

AbstractMalaria transmission-blocking vaccines (TBVs) are a critical tool for disease elimination. TBVs prevent completion of the developmental lifecycle of malarial parasites within the mosquito vector, effectively blocking subsequent infections. The mosquito midgut protein Anopheline alanyl aminopeptidase N (AnAPN1) is the leading, mosquito-based TBV antigen and structure-function studies have identified two Class II epitopes that induce potent transmission-blocking (T-B) antibodies. Here, we functionally screened new immunogens and down-selected to the UF6b construct that has two glycine-linked copies of the T-B epitopes. We established a process for manufacturing UF6b and evaluated in outbred female CD1 mice the immunogenicity of the preclinical product with the human-safe adjuvant Glucopyranosyl Lipid Adjuvant in a liposomal formulation with saponin QS21 (GLA-LSQ). UF6b:GLA-LSQ was immunogenic and immunofocused the humoral response to one of the key T-B epitopes resulting in potent T-B activity and establishing UF6b as a prime TBV candidate to aid in malaria elimination and eradication efforts.


2014 ◽  
Vol 17 (3) ◽  
pp. 421-426 ◽  
Author(s):  
B. Tokarz-Deptuła ◽  
P. Niedźwiedzka-Rystwej ◽  
B. Hukowska-Szematowicz ◽  
M. Adamiak ◽  
A. Trzeciak-Ryczek ◽  
...  

Abstract In Poland, rabbit is a highly valued animal, due to dietetic and flavour values of its meat, but above all, rabbits tend to be commonly used laboratory animals. The aim of the study was developing standards for counts of B-cells with CD19+ receptor, T-cells with CD5+ receptor, and their subpopulations, namely T-cells with CD4+, CD8+ and CD25+ receptor in the peripheral blood of mixed-breed Polish rabbits with addition of blood of meet breeds, including the assessment of the impact of four seasons of the year and animal sex on the values of the immunological parameters determined. The results showed that the counts of B- and T-cells and their subpopulations in peripheral blood remain within the following ranges: for CD19+ B-cells: 1.05 - 3.05%, for CD5+ T-cells: 34.00 - 43.07%, CD4+ T-cells: 23.52 - 33.23%, CD8+ T-cells: 12.55 - 17.30%, whereas for CD25+ T-cells: 0.72 - 2.81%. As it comes to the season of the year, it was observed that it principally affects the values of CD25+ T-cells, while in the case of rabbit sex, more changes were found in females.


Antibiotics ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 335
Author(s):  
Anssi Karvonen ◽  
Ville Räihä ◽  
Ines Klemme ◽  
Roghaieh Ashrafi ◽  
Pekka Hyvärinen ◽  
...  

Environmental heterogeneity is a central component influencing the virulence and epidemiology of infectious diseases. The number and distribution of susceptible hosts determines disease transmission opportunities, shifting the epidemiological threshold between the spread and fadeout of a disease. Similarly, the presence and diversity of other hosts, pathogens and environmental microbes, may inhibit or accelerate an epidemic. This has important applied implications in farming environments, where high numbers of susceptible hosts are maintained in conditions of minimal environmental heterogeneity. We investigated how the quantity and quality of aquaculture enrichments (few vs. many stones; clean stones vs. stones conditioned in lake water) influenced the severity of infection of a pathogenic bacterium, Flavobacterium columnare, in salmonid fishes. We found that the conditioning of the stones significantly increased host survival in rearing tanks with few stones. A similar effect of increased host survival was also observed with a higher number of unconditioned stones. These results suggest that a simple increase in the heterogeneity of aquaculture environment can significantly reduce the impact of diseases, most likely operating through a reduction in pathogen transmission (stone quantity) and the formation of beneficial microbial communities (stone quality). This supports enriched rearing as an ecological and economic way to prevent bacterial infections with the minimal use of antimicrobials.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ying Zhang ◽  
Yijie Huang ◽  
Tao Ai ◽  
Jun Luo ◽  
Hanmin Liu

Abstract Background Following the outbreak of the COVID-19 pandemic, a change in the incidence and transmission of respiratory pathogens was observed. Here, we retrospectively analyzed the impact of COVID-19 on the epidemiologic characteristics of Mycoplasma pneumoniae infection among children in Chengdu, one of the largest cities of western China. Method M. pneumoniae infection was diagnosed in 33,345 pediatric patients with respiratory symptoms at the Chengdu Women’s & Children’s Central Hospital between January 2017 and December 2020, based on a serum antibody titer of ≥1:160 measured by the passive agglutination assay. Differences in infection rates were examined by sex, age, and temporal distribution. Results Two epidemic outbreaks occurred between October-December 2017 and April-December 2019, and two infection peaks were detected in the second and fourth quarters of 2017, 2018, and 2019. Due to the public health response to COVID-19, the number of positive M. pneumoniae cases significantly decreased in the second quarter of 2020. The number of M. pneumoniae infection among children aged 3–6 years was higher than that in other age groups. Conclusions Preschool children are more susceptible to M. pneumoniae infection and close contact appears to be the predominant factor favoring pathogen transmission. The public health response to COVID-19 can effectively control the transmission of M. pneumoniae.


2001 ◽  
Vol 17 (suppl) ◽  
pp. S155-S164 ◽  
Author(s):  
Pedro F. C. Vasconcelos ◽  
Amélia P. A. Travassos da Rosa ◽  
Sueli G. Rodrigues ◽  
Elizabeth S. Travassos da Rosa ◽  
Nicolas Dégallier ◽  
...  

A total of 187 different species of arboviruses and other viruses in vertebrates were identified at the Evandro Chagas Institute (IEC) from 1954 to 1998, among more than 10,000 arbovirus strains isolated from humans, hematophagous insects, and wild and sentinel vertebrates. Despite intensive studies in the Brazilian Amazon region, especially in Pará State, very little is known about most of these viruses, except for information on date, time, source, and method of isolation, as well as their capacity to infect laboratory animals. This paper reviews ecological and epidemiological data and analyzes the impact of vector and host population changes on various viruses as a result of profound changes in the natural environment. Deforestation, mining, dam and highway construction, human colonization, and urbanization were the main manmade environmental changes associated with the emergence and/or reemergence of relevant arboviruses, including some known pathogens for humans.


Vaccines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 33
Author(s):  
Marie-Eve Laliberté-Gagné ◽  
Marilène Bolduc ◽  
Caroline Garneau ◽  
Santa-Mariela Olivera-Ugarte ◽  
Pierre Savard ◽  
...  

Background: The papaya mosaic virus (PapMV) vaccine platform is a rod-shaped nanoparticle made of the recombinant PapMV coat protein (CP) self-assembled around a noncoding single-stranded RNA (ssRNA) template. The PapMV nanoparticle induces innate immunity through stimulation of the Toll-like receptors (TLR) 7 and 8. The display of the vaccine antigen at the surface of the nanoparticle, associated with the co-stimulation signal via TLR7/8, ensures a strong stimulation of the immune response, which is ideal for the development of candidate vaccines. In this study, we assess the impact of where the peptide antigen is fused, whether at the surface or at the extremities of the nanoparticles, on the immune response directed to that antigen. Methods: Two different peptides from influenza A virus were used as model antigens. The conserved M2e peptide, derived from the matrix protein 2 was chosen as the B-cell epitope, and a peptide derived from the nucleocapsid was chosen as the cytotoxic T lymphocytes (CTL) epitope. These peptides were coupled at two different positions on the PapMV CP, the N- (PapMV-N) or the C-terminus (PapMV-C), using the transpeptidase activity of Sortase A (SrtA). The immune responses, both humoral and CD8+ T-cell-mediated, directed to the peptide antigens in the two different fusion contexts were analyzed and compared. The impact of coupling density at the surface of the nanoparticle was also investigated. Conclusions: The results demonstrate that coupling of the peptide antigens at the N-terminus (PapMV-N) of the PapMV CP led to an enhanced immune response to the coupled peptide antigens as compared to coupling to the C-terminus. The difference between the two vaccine platforms is linked to the enhanced capacity of the PapMV-N vaccine platform to stimulate TLR7/8. We also demonstrated that the strength of the immune response increases with the density of coupling at the surface of the nanoparticles.


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