The rod-shaped bacteria of the genus Salmonella are a common cause of intestinal illness globally, posing a significant public health threat. These bacteria cause a spectrum of diseases, ranging from mild, self-limiting food poisoning to severe, life-threatening systemic infections. The global health burden associated with salmonellosis is substantial, with an estimated 95 million cases occurring annually, resulting in approximately 150,000 deaths worldwide. The most affected regions are low- and middle-income countries where sanitation and hygiene are often suboptimal. Vaccination has become a necessary preventative measure, especially as the bacteria exhibit a growing resistance to common antibiotics, complicating treatment.
Understanding the Pathogen Targeted by Vaccines
Salmonella bacteria are categorized into two major groupings based on the disease they cause and their host preference. The Typhoidal strains (TS), such as Salmonella Typhi and Salmonella Paratyphi A, are strictly adapted to humans. These strains cause a severe, systemic illness known as enteric fever, or Typhoid fever, which involves the bacteria invading the bloodstream.
In contrast, the non-Typhoidal strains (NTS), which include serovars like Salmonella Typhimurium and Salmonella Enteritidis, are zoonotic and have a broad host range that includes many animals. NTS infections in humans typically result in self-limiting gastroenteritis, commonly referred to as food poisoning. The distinction is crucial: human vaccines focus on preventing the severe Typhoidal fevers, while vaccines for livestock target NTS to prevent their entry into the human food supply.
Human Vaccines and Recommended Administration
Vaccines developed for humans target Typhoid fever and come in several forms. The two long-standing options are the live attenuated oral vaccine and the injectable capsular polysaccharide vaccine.
The live attenuated oral vaccine, Ty21a (Vivotif), is administered as four capsules taken every other day. The full series must be completed at least one week before potential exposure. This vaccine is approved for people aged five and older and provides an efficacy ranging from 50% to 80% for up to seven years.
The Vi capsular polysaccharide vaccine (ViCPS) is an injectable vaccine approved for people two years of age and older. ViCPS is given as a single intramuscular dose, ideally at least two weeks before travel. Protection levels are similar to the oral vaccine, offering 50% to 80% efficacy, but the duration is shorter, requiring a booster dose every two years.
A newer option is the Typhoid Conjugate Vaccine (TCV), which links the Vi polysaccharide to a protein carrier. TCVs are approved for children as young as six months of age and offer a higher efficacy, typically between 79% and 85%, with protection lasting at least four years. Vaccination is primarily recommended for individuals traveling to or living in high-risk areas, such as South Asia, Africa, and Latin America, as well as laboratory personnel who handle the bacteria.
How the Vaccines Work to Create Immunity
The different vaccine formulations generate immunity through distinct immunological pathways. The live attenuated oral vaccine, Ty21a, uses a weakened strain of S. Typhi that is still capable of invading the intestinal lining, mimicking a natural infection. This approach stimulates both the humoral immune response, which produces antibodies, and the cellular immune response involving T-cells. T-cell activation is important for long-term immunological memory and is considered robust against intracellular pathogens like Salmonella.
The Vi capsular polysaccharide vaccine (ViCPS), conversely, contains only the purified Vi antigen from the bacterial surface. This antigen triggers an immune response that is largely T-cell-independent, meaning it directly stimulates B-cells to produce antibodies, primarily Immunoglobulin M (IgM). This response results in limited immunological memory and requires frequent booster shots.
The newer Typhoid Conjugate Vaccines (TCVs) overcome this limitation by chemically linking the Vi polysaccharide to an inert protein. This carrier protein converts the response into a T-cell-dependent process, allowing for the generation of long-lasting memory B-cells and the production of high-affinity Immunoglobulin G (IgG) antibodies.
Vaccination as a Strategy for Food Safety
The application of Salmonella vaccines in livestock represents a public health measure aimed at preventing disease transmission to humans through the food chain. In animals like poultry and cattle, the goal of vaccination is not primarily to protect the animals from severe illness, but rather to reduce the pathogen load they carry. By targeting non-Typhoidal Salmonella serovars, such as S. Typhimurium and S. Enteritidis, the vaccines limit the colonization of the bacteria in the animals’ gut and reproductive systems.
Reducing colonization prevents the bacteria from contaminating meat and eggs, which are major sources of human infection. Both live attenuated and inactivated vaccines are employed in poultry operations. Live vaccines are often preferred because they induce a stronger, cross-protective immune response involving both cellular and humoral immunity. In cattle, vaccines are developed to reduce Salmonella prevalence in the feces and peripheral lymph nodes, which can contaminate meat during processing. This “pre-harvest” intervention complements farm biosecurity efforts to safeguard the human food supply.