**1. Introduction**

The phylum Nematoda consists of non-segmented invertebrates commonly known as roundworms that occur in a wide range of habitats around the globe and lack jointed appendages. The causative agent of *trichinellosis* is *Trichinella* species including *Trichinella spiralis* (*T. spiralis*) which belongs to the superfamily Trichinelloidea of the phylum Nematoda. At present, the recognized number of species and genotypes in the genus *Trichinella* are nine and three respectively based on the larvae appearance in muscle cells [1, 2]. The most pathogenic and prevalent pathogen in this genus is *T. spiralis* [3]. This is a most serious zoonotic food-borne parasite which can infect a wide range of hosts, is liable for *trichinellosis* disease in humans, and can infect more than 150 species of animals such as carnivores and omnivores including human beings worldwide [4, 5]. *Trichinellosis* occurs around many parts of the world and infects a huge number of human beings. Its ranges from Europe, North America, China, Japan, and Tropical Africa. However, China is the most affected country [1, 6].

The definitive hosts of nematode *Trichinella* include many domestic animals such as pigs, horses, and wild animals like bears, rats, and wild pigs. Each intermediate host of *Trichinella spiralis* is also its definitive host and serves as a source of infection for any other definitive host species by carnivorism [2]. Humans can acquire infection by the ingestion of undercooked, or raw meat of these animals contaminated with the larvae of *T. spiralis* [7]. The important preventive measure (to limit people from getting *trichinellosis*) is to disrupt the transmission of infective *Trichinella* larvae encapsulated in meat to human beings [8, 9]. However, in some countries, this disease is also transmitted by wild animals [10]. Since an enormous amount of pork and its by-products are consumed in China, that results in increased issues in the country [5, 11]. Unlike many other helminth parasites, the survival of *T. spiralis* nematodes is only direct host-to-host transmission adapting normal cellular functions and host immunity at all the stages of infection [12, 13].

The life cycle of *T. spiralis* starts when an adult female and male worms reproduce sexually in the small intestine of the host. The unique characteristic of *T. spiralis* among other parasites is that it passes all the stages of its life cycle within a single host including all phases of adult worm, newborn larvae, and muscle larvae [10, 14, 15]. Humans acquire the infection when they ingest *Trichinella* larvae that are encapsulated in the striated muscles of domestic or wild animals [5]. After the consumption of infected meat, parasitic larvae which are encysted in the meat are then released into the host stomach by acid-pepsin digestion [16]. Columnar epithelial cells of the intestine at the base of the villus are invaded by muscular larvae. Previously released into the stomach from meat and each molts four times to reach sexual maturity [7, 9, 17]. Approximately 1500 newborn larvae are produced by each fertilized female *T. spiralis* within 2–3 weeks and up to 10,000 over 4 months period. These larvae penetrate the intestinal lining with the help of unique sword-like stylet they possess and migrate to the striated (skeletal) muscles via the circulatory and lymphatic system [15]. These larvae can enter any type of cells but only survive in skeletal muscles. In the striated muscles, these previously migrated newborn larvae develop into infective muscle larvae and transform the skeletal muscle cells into a new type of cells known as nurse cells which maintain the larval life and for many species of *Trichinella* changes into capsules or cysts made up of hyaline and collagen fiber [8]. These capsules containing the muscle larvae can persist for many years and calcification occurs in most of the cysts and dies within a few months (see **Figure 1**). The life span of live adult worms in the mucosa of the intestine is 4–6 weeks in human beings while the muscle larvae encapsulated in the striated muscle fibers persist for months to years [1].

Immunity is the defensive mechanism against any pathogenic organisms that invade the victimized host. When the host consumes contaminated meat containing nurse cells, an immune-mediated inflammatory response starts due to the development of the adult worms in the epithelium of the intestine to expel the parasites. The *Perspective Chapter: Advances in the Development of Anti-*Trichinella spiralis *Vaccine… DOI: http://dx.doi.org/10.5772/intechopen.103027*

**Figure 1.** *Life cycle of* T. spiralis *[10].*

level of antibody IgE which defends the body against parasitic organisms starts to increase. The inflammatory infiltrates containing mast cells and eosinophils present there pathologically. Both these immune cells are involved in the clearance of parasites. Toxic oxygen molecules and major basic proteins are elaborated by eosinophil to kill invaded organisms but also cause to damage the host body tissues. While mast cell protease-1 (MCP-1) is produced by mast cells that are also lethal to worms. There is widespread inflammation, edema if worm load is high and cells death occurs frequently during the parenteral stage of infection [18, 19].

Trichinellosis infection is classified into three stages depending upon the life cycle of the pathogenic worm; **(1)** as an **invasive stage**, in which larvae grow into adult worms and after fertilization females begin to release newborn larvae which then migrate to blood circulation via the Lymphatic system [9]. This stage is characterized by nausea, diarrhea, abdominal cramps, and seldom vomiting. Constipation is also seen in some of the individuals instead of diarrhea. All these symptoms appear within 2–30 h of post-eating infected food. **(2)** As **migratory phase**; characterized by the encapsulation of larvae in the muscles of the host. The main symptoms observed in this stage include fever, face edema, swelling, muscle pain, and weakness of the infected muscles [14, 16]. (3) As **encystment stage**; characterized by the calcification of cysts in the striated muscles only and results in everlasting injury [1]. As this parasite shows nonspecific signs and symptoms of the disease, its clinical diagnosis is difficult [15]. For the diagnosis of *Trichinellosis*, the digestion method

is the best method reported by World Organization for Animal Health (OIE) but to better detect the *Trichinella* parasites molecular biology and serologic methods have been developed [5]. Currently, *Trichinellosis* diagnosis is based on larvae detection in muscle biopsy or immunodiagnostic tests which are highly specific. Many antigens are expressed during the developmental stages of the *T. spiralis* and are useful for the serodiagnosis of *trichinellosis*. However, due to limited *T. spiralis* antigens availability testing is not extensively available [15, 16].

*Trichinellosis* is not only responsible for public health casualties but also cause the economic problem in food safety and swine animal production. Due to a large number of people infected with *T. spiralis*, this disease is regarded as re-emerging in many regions of the world [2, 15]. If transmission of this disease is not under control, it can lead to serious public health problems [10].

### **2. Status of anti-***T. spiralis* **vaccine**

It is a promising method for the control of parasites in pigs to develop a vaccine against *T. spiralis* infection. However, most of the studies for the development of vaccines against *Trichinella* have been performed in lab animals (Mouse models) so far. Only a few studies are performed on pigs for the development of vaccines against *Trichinella* infection. To prevent and control the transmission of *T. spiralis* infection from pigs to humans vaccine exploitation is an important step [20]. *Trichinella* is a tissue-lodging, enteral, and multicellular parasite. Its life cycle is complex and has a diverse developmental phase. *Trichinella* worms have stage-specific antigens [21]. It is necessary to develop an effective vaccine against *Trichinella* to interrupt the transmission of parasites among animals and the cycle of pathogen transmission from swine to humans [5].

Till now, various practices and strategies have been used in the prevention and eradication of parasites including the application of chemicals. The chemical methods are not well signed and have certain limitations such as continuous use of antiparasitic drugs resulting in rising resistance, have risks related to the environment, health, and their potential effects on the host or non-target organisms. Chemotherapy and antiparasitic drugs are used to prevent *T. spiralis* infection, but when we compare the vaccination of animals with chemotherapy treatment, we found that it has several advantages. A single dose of vaccine can provide lifelong prevention of *T. spiralis* infection, reduce the risk of drug residues in meat and other by-products, and decline the emergence of *T. spiralis* drug-resistant parasites [2].

Anti-*Trichinella* vaccines will provide a substantial contribution to the control, prevention, and elimination of *Trichinellosis*. The eradication of *Trichinella* spp. infections in animals is a difficult task as vaccines against *Trichinella* that act as a preventive weapon are not currently available except for rats and pig models [6]. For the past three decades, significant improvements have been made for the recognition of several antigens from *T. spiralis*. It will lead toward a better understanding of the formulation of novel vaccine developments. A variety of vaccines such as subunit vaccines, recombinant proteins vaccines, inactivated vaccines, synthesized epitope vaccines, DNA vaccines, viral or bacterial vector vaccines can elicit an immune response against *Trichinella* and provide effective protection. Scientists have used different antigens to formulate recombinant protein vaccines and many of them have provided some effective protection against *Trichinella* infection [4, 10].

Preventive vaccine development against *Trichinella* infection in domestic pigs is valuable to control and prevent this parasite [21]. The diseases can also be controlled *Perspective Chapter: Advances in the Development of Anti-*Trichinella spiralis *Vaccine… DOI: http://dx.doi.org/10.5772/intechopen.103027*

in animals through a veterinary vaccine. To induce long-term intestinal immunity the appropriate route for immunization against *Trichinellosis* is oral as the infection occurs due to the ingestion of poorly cooked meat containing encapsulated infective larvae [20]. Proteases (enzymes) are widely distributed in viruses, prokaryotes, and eukaryotes participate in different events of the parasite's life cycle. In the process of causing infection, parasites serine proteases are thought to be a key factor and exist in the *T. spiralis* excretory-secretory (ES) products [20, 22]. The hydrolyzing enzyme Elastase (trypsin-like serine protease) helps the parasites in the penetration of host tissue through the hydrolysis of laminin, fibronectin, elastin, and type IV collagen. Elastases also participate in the immune evasion process. This enzyme is also involved in the digestion and molting of parasites and has an important role in parasitic worm intrusion of victimized hosts. It might be a target for a novel vaccine [21]. Recently, many anti-*T. spiralis* vaccines have been developed to interrupt the transmission of parasites from animals to humans. Many vaccine candidates which are effective against *T. spiralis* were selected from ES products and recombinant proteins. Serine protease enzymes (from *T. spiralis*) provide partial protection against *T. spiralis* larvae challenges [20].

*T. spiralis* exerts an immunomodulatory effect through ES products on the immune response of the host [22]. *T. spiralis* Nudix hydrolase (TsND) is a protein that binds to intestinal epithelial cells of normal mice (up-regulated gene). The size of this gene is about 1248 bp. A partial protective immunity against *Trichinella* infection was observed when mice were vaccinated with recombinant TsND protein [22, 23]. Vehicle (delivery system) and antigen are important elements that are responsible for the protection level induced by the candidate vaccine [24].
