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Among more than 2500 nontyphoidal Salmonella enterica (NTS) serovars, S. enterica serovar Typhimurium and S. enterica serovar Enteritidis account for approximately fifty percent of all human isolates of NTS reported globally. The global incidence of NTS gastroenteritis in 2010 was estimated to be 93 million cases, approximately 80 million of which were contracted via food-borne transmission. It is estimated that 155,000 deaths resulted from NTS in 2010. NTS also causes severe, extra-intestinal, invasive bacteremia, referred to as invasive nontyphoidal Salmonella (iNTS) disease. iNTS disease usually presents as a febrile illness, frequently without gastrointestinal symptoms, in both adults and children. Symptoms of iNTS are similar to malaria, often including fever (>90%) and splenomegaly (>40%). The underlying reasons for the high rates of iNTS disease in Africa are still being elucidated. Evidence from animal and human studies supports the feasibility of developing a safe and effective vaccine against iNTS. Both antibodies and complement can kill Salmonella species in vitro . Proof-of-principle studies in animal models have demonstrated efficacy for live attenuated and subunit vaccines that target the O-antigens, flagellin proteins, and other outer membrane proteins of serovars Typhimurium and Enteritidis. More recently, a novel delivery strategy for NTS vaccines has been developed: the Generalized Modules for Membrane Antigens (GMMA) technology which presents surface polysaccharides and outer membrane proteins in their native conformation. GMMA technology is self-adjuvanting, as it delivers multiple pathogen-associated molecular pattern molecules. GMMA may be particularly relevant for low- and middle-income countries as it has the potential for high immunologic potency at a low cost and involves a relatively simple production process without the need for complex conjugation. Several vaccines for the predominant NTS serovars Typhimurium and Enteritidis, are currently under development. [ABSTRACT FROM AUTHOR]

Highlights: [ • ] An attenuated nontyphoidal Salmonella live oral vaccine is designed by deleting genes guaBA and clpP. [ • ] We test the safety of this vaccine in monkeys infected with simian immunodeficiency virus. [ • ] The vaccine was safe and well-tolerated, establishing basis for efficacy and protection studies. [Copyright &y& Elsevier]

Abstract: Non-typhoidal Salmonella enterica (NTS) serovars Typhimurium and Enteritidis are important causes of bacterial gastroenteritis in the USA and worldwide. In sub-Saharan Africa these two serovars are emerging as agents associated with lethal invasive disease (e.g., bacteremia, meningitis). The development of NTS vaccines, based on mucosally administered live attenuated strains and parenteral non-living antigens, could diminish the NTS disease burden globally. Mouse models of S. Typhimurium and S. Enteritidis invasive disease can accelerate the development of NTS vaccines. Live attenuated NTS vaccines elicit both cellular and humoral immunity in mice and their efficacy is well established. In contrast, non-living vaccines that primarily elicit humoral immunity have demonstrated variable efficacy. An analysis of the reported studies with non-living vaccines against S. Typhimurium and S. Enteritidis reveals that efficacy is influenced by two important independent variables: (1) the innate susceptibility to NTS infection that differs dramatically between commonly used mouse strains and (2) the virulence of the NTS strain used for challenge. Protection by non-living vaccines has generally been seen only in host–pathogen interactions where a sub-lethal infection results, such as challenging resistant mice with either highly virulent or weakly virulent strains or susceptible mice with weakly virulent strains. The immunologic basis of this discrepancy and the implications for human NTS vaccine development are reviewed herein. [Copyright &y& Elsevier]

Salmonella enterica serovar Typhi produces significant morbidity and mortality worldwide despite the fact that there are licensed Salmonella Typhi vaccines available. This is primarily due to the fact that these vaccines are not used in the countries that most need them. There is growing recognition that an effective invasive Salmonella vaccine formulation must also prevent infection due to other Salmonella serovars. We anticipate that a multivalent vaccine that targets the following serovars will be needed to control invasive Salmonella infections worldwide: Salmonella Typhi, Salmonella Paratyphi A, Salmonella Paratyphi B (currently uncommon but may become dominant again), Salmonella Typhimurium, Salmonella Enteritidis and Salmonella Choleraesuis (as well as other Group C Salmonella ). Live attenuated vaccines are an attractive vaccine formulation for use in developing as well as developed countries. Here, we describe the methods of attenuation that have been used to date to create live attenuated Salmonella vaccines and provide an update on the progress that has been made on these vaccines. [ABSTRACT FROM AUTHOR]

Older adults are more susceptible to viral and bacterial infection, and experience higher incidence and severity of infectious diseases. Although vaccination is the most logical solution in preventing infectious diseases, primary vaccine responses in individuals aged ≥65 years-old fail to generate complete protection. This is presumably attributed to immunosenescence, a term that describes functional differences associated with the immune system and natural age advancement. Both the innate and adaptive immune systems experience age-related impairments that contribute to insufficient protection following vaccination. This review addresses current knowledge of age-related changes that affect vaccine responsiveness; including the deficits in innate cell functions, dampened humoral and cell-mediated immune responses, current vaccination schedules for older adults, and concludes with potential strategies for improving vaccine efficacy specifically for this age group. Due to an age-related decline in immunity and poor vaccine responses, infectious diseases remain a burden among the aged population. [ABSTRACT FROM AUTHOR]

Salmonella enterica serovars Typhi and Paratyphi ( S . Paratyphi) A and B cause enteric fever in humans. Of the paratyphoid group, S . Paratyphi A is the most common serovar. In 2000, there were an estimated 5.4 million cases of S . Paratyphi A worldwide. More recently paratyphoid fever has accounted for an increasing fraction of all cases of enteric fever. Although vaccines for typhoid fever have been developed and in use for decades, vaccines for paratyphoid fever have not yet been licensed. Several S . Paratyphi A vaccines, however, are in development and based on either whole cell live-attenuated strains or repeating units of the lipopolysaccharide O-antigen (O:2) conjugated to different protein carriers. An O-specific polysaccharide (O:2) of S . Paratyphi A conjugated to tetanus toxoid (O:2-TT), for example, has been determined to be safe and immunogenic after one dose in Phase I and Phase II trials. Two other conjugated vaccine candidates linked to diphtheria toxin and a live-attenuated oral vaccine candidate are currently in preclinical development. As promising vaccine candidates are advanced along the development pipeline, an adequate supply of vaccines will need to be ensured to meet growing demand, particularly in the most affected countries. [ABSTRACT FROM AUTHOR]