Vaccine composition for use against salmonella choleraesuis infection

Abstract

The present invention relates to the use of a live attenuated Salmonella Typhimurium bacterium for cross protecting pigs, in particular piglets, against Salmonella Choleraesuis infection. The present invention is particularly suited to reduced mortality rate and / or to improve ADWG of piglets from an herd experiencing a Salmonella Choleraesuis outbreak.

Description

[0001] Vaccine composition for use against Salmonella Choleraesuis infection

[0002] Field of the invention

[0003] The present invention relates to a vaccine composition to be used for protecting pigs, in particular piglets, against Salmonella Choleraesuis infection. More particularly, the present invention relates to the use of a vaccine composition comprising live attenuated Salmonella Typhimurium bacteria for cross protection against another serotype of Salmonella, in particular against Salmonella Choleraesuis.

[0004] Background of the invention

[0005] Salmonellosis of swine is one of the most economically important enteric and septicemic diseases affecting young pigs. Among the 2,400 Salmonella serotypes, there a two host adapted serotypes infecting pigs: Salmonella Choleraesuis and Typhisuis, and non-host adapted serotypes Typhimurium and Salmonella Derby, that play a major role in infections in pigs. Salmonellosis is characterized clinically by one or more of three major symptoms: septicemia, acute enteritis and chronic enteritis. The prevalence of infection varies among species and countries and is much higher than the incidence of clinical disease, which is commonly precipitated by stressful situations such as sudden deprivation of feed, transportation, drought, crowding, parturition and the administration of some drugs.

[0006] Septicemic salmonellosis is often associated with Salmonella Choleraesuis. Salmonella Choleraesuis is a gram-negative bacterium that typically affects growing pigs less than 5 months of age by colonizing the intestinal tract of pigs, more particularly the colon. The main route of transmission is fecal-oral, as the bacteria are shed rapidly upon infection and up to 5 months post-infection. Generally, Salmonella Choleraesuis causes septicemia in weaned pigs, less than 5 months of age. Occasionally other ages of pigs can be affected. Duration of the disease is highly variable. The first symptom seen in infected pigs is fever, accompanied by lethargy and anorexia. While the morbidity rate is of about 10%, cases tend to be fatal. Sudden death is therefore quite common with pigs showing signs of cyanosis on the extremities: blue ears are often seen. In the next days following infection, yellow diarrhea and coughing may be seen.

[0007] Clinical signs severity and duration of Salmonella Choleraesuis infection can be decreased through aggressive antimicrobial therapy early in the onset of the disease. Typically drugs such as apramycin, ceftiofur, trimethoprim-sulfonamide, or gentamicin can be used. However, it is important to monitor for antimicrobial resistance, as this is common in all Salmonella strains. Therefore, strong and efficient vaccine strategies are required to prevent or reduce Salmonella Choleraesuis recrudescence in herds.

[0008] Summary of the invention

[0009] By working on the development of vaccination strategy to protect swine against Salmonellosis, the inventors have shown that an avirulent live vaccine comprising Salmonella Typhimurium bacteria may be efficiently used to protect pigs, and in particular piglets, against Salmonella Choleraesuis infection. More surprisingly, the inventors have shown that a vaccination with avirulent live vaccine comprising Salmonella Typhimurium bacteria allows to reduce the mortality rate and / or to improve the average daily weight gain (ADWG) of piglets in a herd experiencing an outbreak of Salmonella Choleraesuis.

[0010] It is therefore an object of the present invention to provide vaccine composition comprising live attenuated Salmonella Typhimurium bacteria for use in a method for lessening the severity of symptoms associated with Salmonella Choleraesuis infection and / or for preventing Salmonella Choleraesuis infection in a pig.

[0011] In particular, it is an obj ect of the present invention to provide a vaccine composition comprising live attenuated Salmonella Typhimurium bacteria for use in a method for lessening the severity of symptoms associated with Salmonella Choleraesuis infection and / or for preventing Salmonella Choleraesuis infection in a pig, wherein the live attenuated Salmonella Typhimurium bacterium is the sole Salmonella active ingredient of the vaccine composition, and wherein the method for lessening the severity of symptoms associated with Salmonella Choleraesuis infection and / or for preventing Salmonella Choleraesuis infection in a pig consists of the administration of said vaccine composition.

[0012] In a particular embodiment, the method for lessening the severity of symptoms associated with Salmonella Choleraesuis infection and / or for preventing Salmonella Choleraesuis infection in a pig consists of a single administration of the vaccine composition comprising live attenuated Salmonella Typhimurium bacteria.

[0013] In another particular embodiment, the method for lessening the severity of symptoms associated with Salmonella Choleraesuis infection and / or for preventing Salmonella Choleraesuis infection in a pig consists of repeated administrations, i.e., twice or more, of the vaccine composition comprising live attenuated Salmonella Typhimurium bacteria.

[0014] It is another object of the present invention to provide a method for lessening the severity of symptoms associated with Salmonella Choleraesuis infection and / or for preventing Salmonella Choleraesuis infection in a pig, wherein a vaccine composition comprising live attenuated Salmonella Typhimurium bacteria is administered to said pig.

[0015] Advantageously, the method for lessening the severity of symptoms associated with Salmonella Choleraesuis infection and / or for preventing Salmonella Choleraesuis infection in a pig consists of the administration of said vaccine composition.

[0016] In a particular embodiment, the method consists of a single administration of the vaccine composition comprising live attenuated Salmonella Typhimurium bacteria. In another particular embodiment, the method consists of repeated administrations i.e., twice or more, of the vaccine composition comprising live attenuated Salmonella Typhimurium bacteria.

[0017] The present invention further provides the use of live attenuated Salmonella Typhimurium bacteria for the manufacture of a vaccine composition for lessening the severity of symptoms associated with Salmonella Choleraesuis infection and / or for preventing Salmonella Choleraesuis infection in a pig.

[0018] Advantageously, the use consists of the administration of said vaccine composition only.

[0019] In a particular embodiment, the use consists of a single administration of the vaccine composition comprising live attenuated Salmonella Typhimurium bacteria. In another particular embodiment, the use consists of repeated administrations, i.e., twice or more, of the vaccine composition comprising live attenuated Salmonella Typhimurium bacteria.

[0020] Preferably, the live attenuated Salmonella Typhimurium bacterium is the sole Salmonella active ingredient of the vaccine composition. More preferably, the live attenuated Salmonella Typhimurium bacterium is the sole active ingredient, or antigen, of the vaccine composition.

[0021] In particular, the symptoms associated with Salmonella Choleraesuis infection are selected from increased mortality rate and negative impact on average daily weight gain (ADWG).

[0022] In a particular embodiment, the vaccine composition is administered to piglets not older than 6 weeks. Preferably, the vaccine composition is administered to piglets at 3 days of age or later, such as between 3 days and 6 weeks. In particular, the vaccine composition may be administered twice to a piglet between 3 days of age, + / - 1 day, and 4 weeks of age, + / - 7 days. The lag period between the two administrations is for instance of 3 weeks, + / - 3 days.

[0023] The vaccine composition may be administered orally or parenterally. Preferably, the vaccine composition is administered orally, for instance via drinking water. The present invention is particularly suited for pigs, in particular piglets, from a herd with an outbreak of Salmonella Choleraesuis. For instance, the present invention may be implemented with Salmonella seropositive pigs, such as Salmonella Choleraesuis seropositive pigs, in particular Salmonella Choleraesuis seropositive piglets. In a particular embodiment, the present invention may be implemented with piglets having maternally derived &nA-Salmonella antibodies.

[0024] Advantageously, the vaccinated piglets present an increase ADWG during the fattening period as compared to non-vaccinated pig from a herd with an outbreak of Salmonella Choleraesuis. Alternatively or in addition, the vaccinated piglets may present a decrease of mortality rate during the nursery and / or fattening period.

[0025] According to the invention, the vaccine composition is further efficient for the treatment and / or prophylaxis of Salmonella Typhimurium infection.

[0026] In an embodiment, the vaccine composition comprises between 5.108to 5.109CFU of bacteria per dose.

[0027] In an embodiment, the live attenuated Salmonella Typhimurium bacterium comprises an histidine-adenine auxotrophy.

[0028] In an embodiment, the Salmonella Typhimurium bacterium is Salmonella Typhimurium of strain 421 / 125.

[0029] In a particular embodiment, the live attenuated Salmonella Typhimurium bacterium is a nonrecombinant bacterium.

[0030] Legend to the figures

[0031] Figure 1 : Mean mortality rate during nursery (i.e., from birth to about 80 days of age) and fattening (i.e., from about 80 days of age to slaughter) of non-vaccinated and vaccinated piglets from an herd experiencing Salmonella Choleraesuis outbreak.

[0032] Figure 2: Mean ADWG during nursery (i.e., from birth to about 80 days of age) and fattening (i.e., from about 80 days of age to slaughter) of non-vaccinated and vaccinated piglets from an herd experiencing Salmonella Choleraesuis outbreak, in g / day.

[0033] Detailed description of the invention

[0034] The present invention is based on the discovery that a vaccine composition comprising exclusively live attenuated Salmonella Typhimurium as active ingredient may be efficiently used to protect pigs against another Salmonella serotype infection, in particular against Salmonella Choleraesuis infection. More particularly, the inventors have shown that vaccination of piglets with live attenuated Salmonella Typhimurium vaccine composition allows to reduce the mortality rate and / or to increase the average daily weight gain of vaccinated piglets as compared to unvaccinated piglets. The vaccination may be implemented with infected piglets as well as noninfected piglets. Advantageously, the vaccination is implemented in a herd that experiences an outbreak of Salmonella Choleraesuis. That is to say that the animals, in particular swine and piglets, may be infected, e.g., clinically or subclinically infected, or noninfected at the time of the vaccination. The vaccination allows to protect vaccinated animals against Salmonella Choleraesuis, i.e., to prevent infection and / or to reduce the severity of symptoms associated with Salmonella Choleraesuis infection. Advantageously, the vaccination regimen of the present invention comprises exclusively the administration of the above described vaccine composition. That is to say that protection or prevention against Salmonella Choleraesuis infection and / or reduction in the severity of symptoms associated with Salmonella Choleraesuis infection is achieved without administration of a vaccine composition comprising Salmonella Choleraesuis antigen, either whole cell Salmonella Choleraesuis bacterium (attenuated or inactivated) or recombinant and / or isolated Salmonella Choleraesuis antigen. According to the present invention, the pigs do not receive antigens from Salmonella Choleraesuis at all.

[0035] Definitions

[0036] As used herein, the terms “Salmonella Choleraesuis” refer to Salmonella enterica serotype Choleraesuis. The terms “Salmonella Typhimurium” refer to Salmonella enterica serotype Typhimurium.

[0037] As used herein, the terms “treatment” , “treat” or “treating” refer to any act intended to ameliorate the health status of subjects, in particular pigs, including piglets, such as therapy, prevention, prophylaxis and retardation of a disease, in particular a bacterial infection. In certain embodiments, such terms refer to the amelioration or eradication of the disease, or symptoms associated with it. In other embodiments, this term refers to minimizing the spread or worsening of the disease, resulting from the administration of one or more therapeutic agents to a subject with such a disease.

[0038] As used herein, the term “therapeutic effect” refers to an effect induced by a vaccine composition according to the invention, capable to prevent or to delay the appearance of a disease, or to cure or to attenuate the effects of a disease.

[0039] The terms “quantity,” “amount” and “dose” are used interchangeably herein and may refer to an absolute quantification of a molecule or bacterium. The term “attenuated bacterium" or “avirulent bacterium" as used herein refers to a modified bacterial cell the virulence of which has been reduced or weakened but still capable of provoking an immune response, for example a humoral or cellular response, in a subject animal that has been administered a composition comprising the attenuated bacterial cell. Attenuated bacterial cells according to the invention are live bacteria.

[0040] The terms "vaccine" or “vaccine composition" as used herein designate a composition which may be used to cause, stimulate or amplify an immune response in an organism, administered for the prevention, amelioration, or treatment of infectious diseases.

[0041] An "immune response" designates the development in a host of a cellular and / or antibody- mediated immune response. Usually, an "immune response" includes the production of antibodies, B cells, helper T cells, and / or cytotoxic T cells, directed specifically to an antigen or antigens of interest. Preferably, the immune response is protective such that resistance to new infection will be enhanced and / or the clinical severity of the disease reduced. For the vaccine according to the invention, the immune response induced in the vaccinated target animal has for instance the effect of reducing infection by Salmonella Choleraesuis. This refers to a reduction of the level or the extent of the infection, for example by reducing the bacterial load or shortening the duration of bacterial replication in the host animal. This effect is obtained e.g., by preventing or reducing the establishment or the proliferation of a productive infection by Salmonella Choleraesuis in its target organs. In turn this leads to a reduction in the target animal of the number, the intensity, or the severity of lesions and clinical signs that could be caused by the bacterial infection. The person skilled in the art is able to determine the effectiveness of a vaccine according to the invention for reducing infection by Salmonella Choleraesuis. For instance, this determination may be done by monitoring the immunological response following vaccination or after a challenge infection, e.g. by monitoring the targets' signs of disease, clinical scores, serological parameters, or by re-isolation of the pathogen, and comparing these results to a vaccination-challenge response seen in mock vaccinated animals.

[0042] In the context of the invention, the expression “between x and ” means that the values x and y are included.

[0043] In the context of the invention, the term “about” means the given value plus or minus 10%.

[0044] Vaccine composition

[0045] It is the purpose of the present invention to provide a vaccine composition, comprising live attenuated Salmonella Typhimurium bacteria as the sole active ingredient or antigen of said vaccine composition, for use to protect pigs against Salmonella Choleraesuis. Indeed, the inventors have discovered that live attenuated Salmonella Typhimurium bacterium may be efficient against Salmonella Choleraesuis infection.

[0046] Any attenuated Salmonella Typhimurium bacterium may be used as active ingredient of the vaccine composition. Advantageously, the Salmonella Typhimurium bacterium is not a recombinant bacterium, i.e., the bacterium does not comprise foreign nucleic acids encoding for a foreign polypeptide or antigen. Thus, the Salmonella Typhimurium bacterium is preferably a non-recombinant Salmonella Typhimurium bacterium. In a particular embodiment, the live attenuated Salmonella Typhimurium bacterium is double attenuated. Preferably live attenuated Salmonella Typhimurium bacterium is histidine-adenine auxotrophic.

[0047] Examples of Salmonella Typhimurium bacteria that may be used for the vaccine composition are described in US 3,856,935.

[0048] In a particular embodiment, the vaccine composition comprises an attenuated Salmonella Typhimurium isolate registered as 421 / 125 by Impfstoffwerk Dessau-Tomau (IDT), Germany and derived from the wild type isolate Salmonella Typhimurium 415 of the Metschnikov Institute, Moscow. The Salmonella Typhimurium 421 / 125 isolate is derived from conventional attenuation chemical mutagenesis (using methylnitroguanidine) and is a modification of the isolate 415 having a deletion within the epimerase gene. In a more particular embodiment, the vaccine composition is SALMOPORC®. The production of the Salmonella Typhimurium isolate 421 / 125 is described in the patent specification DE2843295 C2.

[0049] In a particular embodiment, the live attenuated Salmonella Typhimurium bacteria are the sole Salmonella active ingredients of the vaccine composition. That is to say that the vaccine composition is free of Salmonella of serotype different from Salmonella Typhimurium. In a more particular embodiment, the vaccine composition comprises solely live attenuated Salmonella Typhimurium bacteria as active ingredient, i.e., Salmonella Typhimurium bacteria are the sole ingredients to which an immune response is generated.

[0050] In a particular embodiment, the vaccine composition comprises live attenuated Salmonella Typhimurium bacteria and is free of Salmonella Choleraesuis antigen.

[0051] In a particular embodiment, the vaccine composition consists of live attenuated Salmonella Typhimurium bacteria and optionally suitable carrier and / or adjuvant.

[0052] According to the present invention, the vaccine composition comprises an effective amount of live attenuated Salmonella Typhimurium bacteria. As used herein, the term “ effective amount' refers to a quantity of an active ingredient or of a vaccine composition which prevents, removes or reduces the deleterious effects of the disease. It is obvious that the quantity to be administered can be adapted by the man skilled in the art according to the subject to be treated, to the nature of the disease, etc. In particular, doses and regimen of administration may be function of the nature, of the stage and of the severity of the disease to be treated, as well as of the weight, the age and the global health of the subject to be treated, as well as of the judgment of the veterinarian.

[0053] In a particular embodiment, the vaccine composition comprises between 5.105and 5.1010CFU (Colony Forming Units) of bacteria per dose, for instance between 5.106and 5.1010CFU, between 5.107and 5.109CFU, between 5.106and 5.108CFU. Preferably, the vaccine composition comprises between 5.108and 5.109CFU of bacteria per dose.

[0054] The vaccine composition may also comprise an adjuvant. An “adjuvant” is a compound or combination of compounds that enhance, activate, potentiate, or modulate the quality and / or the quantity of the immune response to an antigen. The choice and amount of adjuvant(s) may be easily determined by the man skilled in the art.

[0055] The vaccine may also include other components, such as preservative(s) and / or stabilizer(s).

[0056] The vaccine composition of the invention may comprise a veterinary acceptable carrier, adjuvant, or combination thereof. Those of skill in the art will recognize that the choice of carrier, adjuvant, or combination will be determined by the delivery route, personal preference, and animal species among other.

[0057] Administration o f the vaccine composition

[0058] According to the present invention, the vaccine composition may be administered to any pigs, including sows and piglets. In a preferred embodiment, the vaccine composition is administered to piglets.

[0059] Advantageously, the pigs or piglets receive solely the vaccine composition of the present invention. That is to say that the pigs or piglets were not previously vaccinated with another Salmonella vaccine composition, in particular a Salmonella vaccine composition comprising Salmonella Choleraesuis antigens, e.g., attenuated or inactivated Salmonella Choleraesuis, and the pigs or piglets will not be vaccinated with another Salmonella vaccine composition later on, either.

[0060] In a particular embodiment, the method for lessening the severity of symptoms associated with Salmonella Choleraesuis infection and / or for preventing Salmonella Choleraesuis infection in a pig consists of a single administration of the vaccine composition comprising a live attenuated Salmonella Typhimurium bacterium.

[0061] In another embodiment, the method for lessening the severity of symptoms associated with Salmonella Choleraesuis infection and / or for preventing Salmonella Choleraesuis infection in a pig consists of repeated administrations, i.e., twice or more, of the vaccine composition comprising a live attenuated Salmonella Typhimurium bacterium. In a preferred embodiment, the vaccine composition is administered to pigs from herd with an outbreak of Salmonella Choleraesuis. By definition, such herd comprises infected animals, e.g., clinically or subclinically infected, or noninfected animals. That is to say that the animals, in particular swine and piglets, may be infected at the time of the vaccination. The vaccine composition may be administered indistinctly to infected and noninfected pigs. Said pigs, in particular said piglets, may be either Salmonella seronegative or Salmonella seropositive. According to the present invention, the vaccination allows to protect vaccinated animals against Salmonella Choleraesuis, i.e., to prevent infection and / or to reduce the severity of symptoms associated with Salmonella Choleraesuis infection. The vaccination may further treat Salmonella Choleraesuis infection in already infected pigs, at least by reducing the severity of symptoms associated with Salmonella Choleraesuis infection.

[0062] The vaccine composition may also be administered to pigs from herd free of Salmonella infection. Said pigs, in particular said piglets, may be either Salmonella seronegative or Salmonella seropositive.

[0063] In a particular embodiment, the vaccine composition is administered to Salmonella seropositive pigs, i.e., which have -Salmonella antibodies, in particular to Salmonella seropositive piglets. Salmonella seropositive pigs encompass pigs already infected by Salmonella and / or pigs already vaccinated against Salmonella. In a particular embodiment, the vaccine composition is administered to Salmonella Choleraesuis seropositive pigs and / or to Salmonella Typhimurium seropositive pigs, in particular to Salmonella Choleraesuis seropositive piglets and / or to Salmonella Typhimurium seropositive piglets.

[0064] In an embodiment, the vaccine composition is administered to piglets having maternally derived wxii-Salmonella antibodies. In particular, the vaccine composition is administered to piglets having maternally derived -Salmonella Choleraesuis antibodies and / or maternally derived &nA-Salmonella Typhimurium antibodies.

[0065] Preferably, the vaccine composition is administered to piglets from an herd experiencing an outbreak of Salmonella Choleraesuis. The vaccination may be implemented with infected piglets as well as noninfected piglets. Both seronegative and seropositive piglets may be vaccinated. Preferably, the vaccine composition is administered to piglets not older than 6 weeks. In the context of the present invention, a week refers to about 7 consecutive days. For instance, the vaccine composition is administered to piglet of 3 days of age or older. When several piglets from a herd are vaccinated, the age of vaccination may correspond to the mean age of the population of piglets.

[0066] Depending on the desired duration and effectiveness of the treatment, the vaccine composition may be administered once or several times, also intermittently, for instance on a daily basis for several days, weeks or months and in different dosages.

[0067] In a particular embodiment, the vaccine composition is administered twice to piglets between 3 days of age, + / - 1 day, and 4 weeks of age, + / - 7 days. For instance, the first administration is performed at 2, 3 or 4 days of age. And the second administration is performed at about 3 weeks of age, 4 weeks of age or 5 weeks of age. In a preferred embodiment, the lag period between the two administrations is of 3 weeks, + / - 3 days. Preferably, the piglets receive one dose of vaccine composition per administration.

[0068] Preferably, the vaccinated pigs or piglets were not vaccinated against Salmonella Choleraesuis before the vaccination with the vaccine composition of the present invention. In particular, the pigs or piglets didn’t receive any vaccine composition comprising Salmonella Choleraesuis antigen.

[0069] Preferably, the vaccinated pigs or piglets will neither receive any vaccine composition comprising Salmonella Choleraesuis antigen, at least for one month, two months or more, after the vaccination with the vaccine composition of the present invention.

[0070] The vaccine composition is administered orally or parenterally. Oral administration includes direct oral administration or oral gavage, and via drinking water, preferably through use of an automatic whole-barn dosing device. In a preferred embodiment, the administration is performed orally via drinking water.

[0071] In a particular embodiment, the vaccine composition is administered twice via drinking water to piglets from an herd experiencing an outbreak of Salmonella Choleraesuis. The first administration is performed at 3 days of age, + / -1 day, and the second administration is performed at 3 weeks of age, + / - 3 days.

[0072] According to the present invention, the vaccine composition comprising live attenuated Salmonella Typhimurium is administered to pigs, in particular to piglets, in order to prevent Salmonella Choleraesuis infection or at least to reduce the severity of symptoms associated to Salmonella Choleraesuis infection.

[0073] As used herein, “prevention” or "reduction of the incidence and / or severity of clinical signs" or "reduction of clinical symptoms" means, but is not limited to, reducing the number of infected animals in a group, reducing or eliminating the number of animals exhibiting clinical signs of infection, or reducing the severity of one or more clinical signs that are present in one or more animals, in comparison to wild-type infection. For example, it should refer to any reduction of pathogen load, pathogen shedding, reduction in pathogen transmission, or reduction of any clinical sign symptomatic of Salmonella Choleraesuis infection. Preferably these clinical signs are reduced in one or more animals receiving the vaccine composition of the present invention by at least 10% in comparison to animals not receiving the vaccine composition and that become infected. More preferably clinical signs are reduced in animals receiving a composition of the present invention by at least 20%, preferably by at least 30%, more preferably by at least 40%, and even more preferably by at least 50%.

[0074] The term "increased protection" herein means, but is not limited to, a statistically significant reduction of one or more clinical symptoms which are associated with infection by Salmonella Choleraesuis in a vaccinated group of subjects vs. a non-vaccinated control group of subjects. The term "statistically significant reduction of clinical symptoms" means, but is not limited to, the frequency in the incidence of at least one clinical symptom in the vaccinated group of subjects is at least 10%, preferably 20%, more preferably 30%, even more preferably 50%, and even more preferably 70% lower than in the non-vaccinated control group after infection by Salmonella Choleraesuis.

[0075] In a preferred embodiment, the administration of the vaccine composition as described above leads to a reduction of mortality rate and / or reduction of loss of weight associated to Salmonella Choleraesuis infection.

[0076] The vaccination according to the present invention is particularly suited to prevent infection and / or to lessen the severity of symptoms associated with Salmonella Choleraesuis infection in piglets. In particular, the vaccination of the present invention allows to significantly reduce the mortality rate and / or negative impact on ADWG in vaccinated piglets submitted to Salmonella Choleraesuis as compared to nonvaccinated piglets submitted to Salmonella Choleraesuis.

[0077] The vaccine composition may also be used to treat Salmonella Choleraesuis infection in infected pigs, by reducing severity of symptoms associated to Salmonella Choleraesuis infection. In an embodiment, said treatment results in the lessening, reduction, and / or cure of Salmonella Choleraesuis infection in pigs, in particular piglets, receiving said vaccine composition. The treatment is selected from the group consisting of reducing signs of diarrhea (shedding), reducing the severity of or incidence of clinical signs of Salmonella Choleraesuis infection, reducing the mortality of pigs from Salmonella Choleraesuis infection, reducing the loss of weight associated to Salmonella Choleraesuis infection and combinations thereof. Preferably, the treatment leads to the reduction of mortality rate and / or reduction of loss weight associated to Salmonella Choleraesuis infection.

[0078] Advantageously, said treatment may also result in the lessening, reduction, prevention and / or cure of Salmonella Typhimurium infection.

[0079] In an embodiment, the vaccine composition is administered to piglets, in order to decrease the mortality rate associated to Salmonella Choleraesuis infection. In particular, the administration of the vaccine composition to piglets of less than 6 weeks of age from a herd with an outbreak of Salmonella Choleraesuis allows to reduce significantly the mortality rate as compared to the mortality rate of unvaccinated piglets from an herd experiencing an outbreak of Salmonella Choleraesuis. Advantageously, the mortality rate of vaccinated piglets from an herd experiencing an outbreak of Salmonella Choleraesuis is similar to the mortality rate of piglets from a herd free of salmonella infection.

[0080] In an embodiment, the mortality rate of vaccinated piglets during the nursery period is decreased as compared to the mortality rate of unvaccinated piglets from an herd experiencing an outbreak of Salmonella Choleraesuis. For instance the mortality rate is reduced by at least 10 %, 20%, 30% , 40%, 50%, 60%, 70%, 80%, 90%, 95%, 97%, 99% relative to piglets that have not received the vaccine composition of the present invention. Alternatively or in addition, the mortality rate of vaccinated piglets during the fattening period may also be decreased as compared to the mortality rate of unvaccinated piglets from an herd experiencing an outbreak of Salmonella Choleraesuis. For instance the mortality rate is reduced by at least 10 %, 20%, 30% , 40%, 50%, 60%, 70%, 80%, 90%, 95%, 97%, 99% relative to piglets that have not received the vaccine composition of the present invention. Preferably, the piglets are vaccinated twice, e.g., at 3 days of age, + / -lday and at 3 weeks of age, + / - 3 days.

[0081] Alternatively or in addition, the vaccine composition is administered to piglets, in order to decrease the negative impact associated to Salmonella Choleraesuis infection on average daily weight gain (ADWG). In particular, the administration of the vaccine composition to piglets of less than 6 weeks of age from a herd with an outbreak of Salmonella Choleraesuis allows to increase significantly their ADWG as compared to the ADWG of unvaccinated piglets from an herd experiencing an outbreak of Salmonella Choleraesuis. Advantageously, the ADWG of vaccinated piglets from an herd experiencing an outbreak of Salmonella Choleraesuis is similar to the ADWG of piglets from a herd free of salmonella infection. Preferably, the piglets are vaccinated twice, e.g., at 3 days of age, + / -lday and at 3 weeks of age, + / - 3 days. Examples

[0082] Experiments were performed in a closed herd in Poland experiencing an Salmonella Choleraesuis outbreak with huge impact on pig health and production parameters.

[0083] Material & Methods

[0084] A 1060 sows herd in Poland experienced an outbreak of Salmonella Choleraesuis. The clinical signs first appeared at the end of rearing and continued in early fattening. The animals showed severe diarrhoea, blue ears, ear necrosis and increased mortality. Salmonella Choleraesuis as cause of disease could be clarified through necropsy (see example 2 below).

[0085] Four groups of about 500 suckling piglets per groups from sows herd experiencing the outbreak of Salmonella Choleraesuis were vaccinated (Vaccinated groups - VACC). Suckling piglets were vaccinated twice orally with a Salmonella Typhimurium (Salmoporc®, Ceva Animal health) live vaccine at 3rdand 21stday, both times 1ml of Salmoporc® by drench.

[0086] Four groups of about 500 suckling piglets per groups from sows herd experiencing the outbreak of Salmonella Choleraesuis were not vaccinated (Negative groups - NEG).

[0087] Results

[0088] The efficacy of the vaccination was assessed by evaluating body weight gain and mortality. More particularly, ADWG and mortality rate were monitored, from birth to the end of the fattening period, corresponding to the age of slaughter.

[0089] The results are summarized in the below tables and figures 1 and 2.

[0090] Table 1 : Production parameters from birth to slaughter (i.e., end of the fattening period)

[0091] The fattening period ends when the animals reach a certain weight (around 117kg, + / - 5 kg). In this trial, the age of the piglets at the end of said fattening period (“Mean age at slaughter”) was significantly reduced from about 210 days for non-vaccinated groups to about 178 days for the vaccinated groups. Therefore, the vaccination of the present invention further leads to improvement of production parameters, leading to a shorter time from birth to slaughter.

[0092] Interestingly, the feed conversion ratio (FCR) representing the ratio of given feed weight over piglet weight gain from birth to slaughter (i.e., feed given / animal weight gain) was also significantly reduced, from 2.845 for the infected-non vaccinated group (NEG) to 2.5175 for the infected-vaccinated group (VACC). Table 2: Mortality rate

[0093] During the outbreak the farms mean losses in nursery were 5.9% and in fattening 7.8%. After the implementation of vaccination, the losses decreased significantly (p<0.001) to 2.3% in nursery and 3.3% in fattening.

[0094] Example 2: Confirmation of outbreak of Salmonella Choleraesuis

[0095] In order to confirm the presence of Salmonella Choleraesuis in the herds, non-vaccinated piglets that died during nursery and fattening period were subjected to necropsy. More particularly, organs (liver, kidney, lung, small and large intestine) from 3 acutely ill animals were examined for Salmonella. Results are summarized in the below table.

[0096] Table 3 : Detection of salmonellae including differentiation of the serovars S. Thyphimurium and S. Choleraesuis by PCR following enrichment by culture

[0097] POS: positive for the corresponding salmonella

[0098] NEG: negative for the corresponding Salmonella In all samples Salmonella Choleraesuis was detected (serotyping: Type C, validation of Salmonella Choleraesuis by PCR).

[0099] In addition, the environment of piglets from different groups during the weaning (at 6 and 9 weeks) and fattening period (at 12, 16 and 20 weeks) was regularly tested for the presence of Salmonella Thyphimurium and other Salmonella that survive in the environment. This is in infected herds more valuable than individual fecal swabs, as the animals shed intermitted and the prevalence has to be very high to be able to detect Salmonella by individual fecal samples. The environmental sampling and Salmonella status assessment were performed according to the method described in K. Lillie-Jaschniski et al. 2023 (Animals 2023, 13, 1031 “Sock and Environmental Swabs as an Efficient, Non-Invasive Tool to Assess the Salmonella Status of Sow Farms”). No presence of Salmonella Typhimurium bacteria has been reported during these tests.

Claims

CLAIMS1. A vaccine composition comprising a live attenuated Salmonella Typhimurium bacterium for use in a method for lessening the severity of symptoms associated with Salmonella Choleraesuis infection and / or for preventing Salmonella Choleraesuis infection in a pig, wherein the live attenuated Salmonella Typhimurium bacterium is the sole Salmonella active ingredient of the vaccine composition, and wherein the method for lessening the severity of symptoms associated with Salmonella Choleraesuis infection and / or for preventing Salmonella Choleraesuis infection in a pig consists of the administration of said vaccine composition.

2. The vaccine composition for use according to claim 1, wherein the method for lessening the severity of symptoms associated with Salmonella Choleraesuis infection and / or for preventing Salmonella Choleraesuis infection in a pig consists of a single administration of the vaccine composition comprising a live attenuated Salmonella Typhimurium bacterium.

3. The vaccine composition for use according to claim 1, wherein the method for lessening the severity of symptoms associated with Salmonella Choleraesuis infection and / or for preventing Salmonella Choleraesuis infection in a pig consists of repeated administrations of the vaccine composition comprising a live attenuated Salmonella Typhimurium bacterium.

4. The vaccine composition for use according to claim 3, wherein the vaccine composition is administered twice to a piglet between 3 days of age, + / - 1 day, and 4 weeks of age, + / - 7 days.5 The vaccine composition for use according to claim 4, wherein the lag period between the two administrations is of 3 weeks, + / - 3 days.

6. The vaccine composition for use according to any one of the previous claims, wherein the symptoms associated with Salmonella Choleraesuis infection are selected from increased mortality rate and negative impact on average daily weight gain (ADWG).

7. The vaccine composition for use according to any one of the previous claims, wherein the vaccine composition is administered to piglet not older than 6 weeks of age.

8. The vaccine composition for use according to any one of the previous claims, wherein the vaccine composition is administered to piglet at 3 days of age or later.

9. The vaccine composition for use according to any one of the previous claims, wherein the vaccine composition is administered orally or parenterally, preferably orally, the oral administration being more preferably performed via drinking water.

10. The vaccine composition for use according to any one of the previous claims, wherein the vaccine composition is administered to a pig, preferably a piglet, from a herd experiencing an outbreak of Salmonella Choleraesuis.

11. The vaccine composition for use according to any one of the previous claims, wherein the vaccine composition is administered to a Salmonella seropositive pig, in particular piglet, preferably a Salmonella Choleraesuis seropositive pigs, in particular piglet.

12. The vaccine composition for use according to any one of the previous claims, wherein the vaccine composition is administered to a piglet having maternally derived anti-Salmonella antibodies.

13. The vaccine composition for use according to any one of the previous claims, wherein the vaccine composition comprises between 5.108to 5.109CFU of bacteria per dose.

14. The vaccine composition for use according to any one of the previous claims, wherein the vaccine composition is administered to piglets from a herd experiencing an outbreak of Salmonella Choleraesuis, and wherein the use results in an increase ADWG during the fattening period as compared to non-vaccinated piglets from a herd experiencing an outbreak of Salmonella Choleraesuis.

15. The vaccine composition for use according to any one of the previous claims, wherein the vaccine composition is administered to piglets from a herd experiencing an outbreak of Salmonella Choleraesuis, and wherein the use results in a decrease of mortality rate as compared to non-vaccinated piglets from a herd experiencing an outbreak of Salmonella Choleraesuis .

16. The vaccine composition for use according to any one of the previous claims, wherein said use further results to the treatment and / or prophylaxis of Salmonella Typhimurium infection.

17. The vaccine composition for use according to any one of the previous claims, wherein the live attenuated Salmonella Typhimurium bacterium comprises an histidine-adenine auxotrophy and / or wherein the Salmonella Typhimurium bacterium is Salmonella Typhimurium of 421 / 125 strain.

18. The vaccine composition for use according to any one of the previous claims, wherein the live attenuated Salmonella Typhimurium bacterium is a non-recombinant bacterium.

19. The vaccine composition for use according to any one of the previous claims, wherein the live attenuated Salmonella Typhimurium bacterium is the sole active ingredient of the vaccine composition.

20. A method for lessening the severity of symptoms associated with Salmonella Choleraesuis infection and / or for preventing Salmonella Choleraesuis infection in a pig, wherein a vaccine composition comprising live attenuated Salmonella Typhimurium bacteria is administered to said pig.

21. Use of live attenuated Salmonella Typhimurium bacteria for the manufacture of a vaccine composition for lessening the severity of symptoms associated with Salmonella Choleraesuis infection and / or for preventing Salmonella Choleraesuis infection in a pig.

22. The method according to claim 20 or the use according to claim 21, which consists of the administration of the vaccine composition comprising the live attenuated Salmonella Typhimurium bacteria only.

23. The method or the use according to claim 22, wherein the live attenuated Salmonella Typhimurium bacteria is the sole active ingredient of the vaccine composition.

24. The method or the use according to claim 22 or 23, wherein the vaccine composition is administered only once to the pig.

25. The method or the use according to claim 22 or 23, wherein the vaccine composition is administered twice or more to the pig.

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