Blood-feeding and digestion are crucial for the tick reproduction because they provide nutrients for anabolic processes such as vitellogenesis, molting and eggs production. Digestion in ticks is mediated by a network of cystein and aspartic peptidases. Therefore, tick digestive peptidases could be a relevant anti-tick vaccine candidates.

Malaria causes almost half a million deaths each year. Existing interventions will almost certainly not be enough to tackle this enormous public health problem on their own. An effective vaccine is urgently needed. The leading malaria vaccine, RTS,S, confers suboptimal protective efficacy, and in addition targets only Plasmodium falciparum and not the other major species of human malaria, P. vivax. This thesis investigates the potential of combining pre-erythrocytic malaria vaccines as a means of enhancing protective efficacy. A novel mathematical model was developed which expresses probability of protection as a function of vaccine-induced humoural and cellular responses. The model predicts that combining partially effective vaccines should result in more than additive improvements in protective efficacy. This was supported by an experiment combining Rv21, a P. vivax circumsporozoite virus-like particle, with viral vectored P. vivax TRAP, the two leading pre-erythrocytic malaria vaccine antigens; this combination raised protective efficacy from 50% and 0%, respectively, to 100% sterile protection. It was also found that antigenic interference, a reduction in anti-CSP titres when Rv21 and PvTRAP are combined, occurred only in the presence of Matrix M adjuvant, and not when using alum, AddaVax or no adjuvant. With a view to creating a single-component multi-antigen vaccine, which would be more cost-effective than a multi-component vaccine, experiments were carried out to establish the virus-like particle Qβ as a platform capable of eliciting protective immunity via the display of short peptides derived from the CSP repeat region of both P. vivax and P. falciparum. For the first time, a tetramer peptide derived from the CSP repeat region of P. vivax VK210, AGDR, was shown capable of eliciting protective immunity alone. Finally, five novel linear B-cell epitopes were discovered, one from P. falciparum CSP, three from P. vivax TRAP and one from TRSP, each capable of conferring partial protection on mice. These epitopes were identified using novel screening methods, using sera from whole-protein vaccinated mice or by exploiting conservation within invasion protein sequences. Two of the protective epitopes, (NANP)6 and (ADGN long) were combined and found to enhance protective efficacy as predicted by the mathematical model. Thus this thesis lays the groundwork for the development of a single-component multi-epitope malaria vaccine with enhanced protective efficacy.

Master of Science in Biomedical Sciences / Department of Diagnostic Medicine/Pathobiology / Alison P. Adams / Salmonella contamination of meat is a leading cause of foodborne illness around the world. Nontyphoidal Salmonella are responsible for an estimated 94 million infections and 155,000 deaths worldwide each year. Of these infections, 86% are estimated to be foodborne. Infection of dairy and beef cattle can lead to contamination of milk and milk products as well as processed beef. Once cattle are infected, Salmonella can be found in many organs of the animals. Peripheral lymph node infections are of particular interest, because these lymph nodes along with hides are the main culprits of meat contamination during processing. Vaccination of production food animals is one of several strategies of prevention and control of Salmonella infections and outbreaks. Vaccination is becoming even more important with the reduction of prophylactic antibiotic use that is driven by an increase in antibiotic resistant bacteria isolated from a variety of food production animals. There are limited commercially available vaccines for cattle that have shown effectiveness, but great strides are being made in this area of research. The vast number of Salmonella serovars with differences in vital virulence factors capable of infecting cattle makes developing vaccines that are cross protective very difficult. This report discusses the known virulence factors of Salmonella, the disease symptoms of bovine salmonellosis, prevention and control strategies, and the development of new vaccines.

No description available.

Acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) are blood cancers that are often treated with stem cell transplantation (SCT). Since SCT treatments have variable success, especially in adults with AML whose disease frequently relapses, novel and more effective solutions must be considered. In this thesis, I will explore one type of immunotherapy in murine models for ALL (L1210) and AML (C1498) using in vitro and in vivo techniques such as flow cytometry and transcriptomics. In my approach, I am attempting to enhance the immunogenicity of whole cell vaccines by pre-infecting the leukemia cells with oncolytic virus (OV) and thus producing leukemia infected cell vaccines (ICVs). While it has been previously shown that L1210-ICV pre-treatment works well in protecting mice from ALL challenge, I have found that pre-immunization with C1498-ICV has a limited efficacy in protecting animals from AML progression. By investigating the downstream effects of ICV, I was able to show that unlike C1498 cells, L1210 cells produce previously unknown immunogenic factors following OV infection.

No description available.

A fundamental challenge in computational vaccinology is that most B-cell epitopes are conformational, and therefore harder to predict. Another significant challenge is that a great deal of the amino acid sequence of a viral surface protein might not in fact be antigenic. Therefore, identifying the regions of a protein that are most promising for vaccine design based on the degree of surface exposure may not lead to a clinically relevant immune response. Linear peptides selected by phage display experiments that have high affinity to the monoclonal antibody of interest usually have similar physicochemical properties to the antigen epitope corresponding to that antibody. The sequences of these linear peptides can be used to find possible epitopes on the surface of the antigen structure or a homology model of the antigen in the absence of an antigen-antibody complex structure. Herein we describe two novel methods for mapping mimotopes to epitopes. The first is an ensemble approach, which combines the prediction results from two existing methods. The second is a novel algorithm named MimoTree, that allows for gaps in the epitopes on the antigen to which the mimotopes match. MimoTree is a fully automated epitope detection algorithm suitable for the identification of conformational as well as linear epitopes. / 2025-01-15T00:00:00Z

Vaccines are one of the greatest modern medical inventions. Even though vaccines have saved lives, however, no medical product is proven to be completely safe. Vaccines can have rare and sometimes deadly reactions. To address such occurrences, the U.S. Department of Health and Human Services (HHS) hosts a program that reviews petitions for compensation of injuries caused by vaccination. The program is called the National Vaccine Injury Compensation Program (VICP). The VICP was established in 1986 to reduce the number of product liability lawsuits against vaccine manufacturers that threatened to increase the cost of vaccines and lower life-saving vaccine administration to millions of people. In 2020, through the Health Resources and Services Administration, the HHS proposed a revision to the VICP. Specifically, the HHS proposed removing an injury called Shoulder Injury Related to Vaccine Administration (SIRVA) from the VICP's no-fault compensation table. The proposed revision of the removal of SIRVA has been the source for debate because it is clear through the establishment of the VICP's founding document that compensation for injuries caused by vaccine administration is required. The HHS is challenging the requirement of compensation for vaccine-related injuries through its proposed revision to the VICP's compensation table. By confronting the HHS's proposal for revision to the Vaccine Injury Table, this thesis demonstrates how existing policy prevents the HHS from making the revision. Using an analysis of precedent statutes and public health research, this thesis argues for the continued coverage of SIRVA with the current VICP.

Staphylococcus aureus (S. aureus) is a frequent cause of infections and sepsis in animals and humans worldwide. Staphylococcal enterotoxins and toxic shock syndrome toxin-1 are bacterial superantigens (SAgs) produced by S. aureus that simultaneously bind to T cell receptor (TCR) and the major histocompatibility complex (MHC) class II, leading to extensive T cell stimulation, release of cytokines, consequently resulting in toxic shock and immunosuppression. In this study, we generated mutant SAgs by introducing alanine substitution at residues involved in interaction with MHC class II and TCR binding and demonstrated attenuation of toxicity in vitro and in vivo. An immunization with mutant SAgs elicits production of neutralizing antibodies against wild type SAgs and protected animals from S. aureus peritonitis at a lethal dose. These results suggest that mutant SAgs will be useful to develop a novel vaccine against S. aureus infections.

No description available.