Efficacy of the intradermal administration of a PRRS vaccine in a swine multicentre field trial

The intradermal vaccination of a live PRRS vaccine (UNISTRAIN® PRRS), through the new needle-free injector Hipradermic®, is an effective and useful tool for the reduction of viraemia and the negative clinical and productive consequences of the PRRS virus in swine under field conditions.
  

Current knowledge on PRRS virus immunology is still limited but it seems clear that modified live PRRS vaccines (MLV) are a reasonable choice for the immunization of pigs. Recently, interest in intradermal vaccination in swine has increased due to research into skin and subcutaneous tissue immunology and the possibility of using needle-free injection devices (NFIDs). The use of NFIDs in the swine industry offers some advantages over conventional needle-and-syringe methods, especially due to the reduced pain and stress to pigs and the increase in the uniformity of the dosage administered to the herd.
The MLV vaccine UNISTRAIN® PRRS has recently obtained the indication for intradermal administration with Hipradermic®, a needle-free injector with connectivity developed by HIPRA for the intradermal vaccination of pigs. A multicentre field trial was conducted under field conditions in order to demonstrate the clinical protection provided by the intradermal administration of UNISTRAIN® PRRS in swine with Hipradermic®.
A multicentre, randomized, double-blind trial was carried out in 1532 pigs distributed between 3 commercial farms (farm Nos. 1, 2 and 3) with a previous history of outbreaks of PRRS. The animals on each farm were randomly divided into two treatment groups. Group A (n=693) was vaccinated once at 3-4 weeks of age (day 0; d0) with 0.2 ml of UNISTRAIN® PRRS vaccine (103.5 CCID50/animal) administered intradermally with Hipradermic®. Group B (n=839) was injected with 0.2 ml PBS (phosphate buffered saline) also intradermally with the same device. All animals included in the trial were individually identified. An outbreak was considered to have occurred when at least 10% of the pigs showed respiratory symptoms and it was confirmed by PCR and serology. The parameters used to assess the efficacy of the vaccine against a PRRS virus outbreak were: viraemia, lesion in PRRS virus positive lungs, clinical respiratory signs, mortality, average daily weight gain (ADWG) and individual number of antibiotics administered throughout the study. Virus detection was carried out by real time RT-qPCR.
A clinical PRRS outbreak was confirmed on two farms (Farm 1: outbreak beginning at day 76 with a PRRSV 95% ORF5 homology; Farm 3: outbreak beginning at day 148 with a PRRSV 88% ORF5 homology) and thus only the results of these two swine farms are shown.
Statistical differences were observed on both farms between the vaccinated and the control group in the reduction in viraemia around and during the outbreak (farm 1: d45 and d90; farm 3: d90, d120 and d150). A statistically better mean clinical index assessment was also observed during the outbreak and specifically on days 76, 78 and 82 (farm 1) and on day 152 on farm 3. Mortality in the fattening period was also statistically reduced.
Percentage of mortality at the fattening unit during the trial:

  

The percentage of lung lesions among PRRSV positive animals (farm 1: 33.3% control vs 63.9% vaccinated; farm 3: 33.3% control vs 90.0% vaccinated) and ADWG from weaning to slaughter were also statistically better in the vaccinated group than in the control group.
ADWG (kg) from weaning to slaughter:

  

On farm 3, a statistical decrease in the percentage of animals treated with antibiotics during the fattening period was also observed.
Percentage of treated animals at fattening unit per farm:

  

The results obtained allow us to conclude that UNISTRAIN® PRRS administered in piglets by the intradermal route through Hipradermic® is effective when administered according to the recommended vaccination program and is a useful tool for the reduction of viraemia and the negative clinical and productive consequences of PRRS virus infection in swine in the field.

Heterologous challenge: Efficacy of the intradermal administration of a PRRS vaccine

  

The intradermal vaccination of a live PRRS vaccine (UNISTRAIN® PRRS), through the new needle-free injector Hipradermic®, is an effective and useful tool to decrease viraemia and thus achieve a reduction in the infection pressure of the PRRS virus on an infected swine farm after a heterologous challenge at 24 weeks post-vaccination.

  

Current knowledge on PRRS virus immunology is still limited but it seems clear that modified live PRRS vaccines (MLV) are a reasonable choice for the immunization of pigs. Recently, interest in intradermal vaccination in swine has increased due to research into skin and subcutaneous tissue immunology and the possibility of using needle-free injection devices (NFIDs). The use of NFIDs in the swine industry offers some advantages over conventional needle-and-syringe methods, especially due to the reduced pain and stress to pigs and the increase in the uniformity of the dosage administered to the herd. Although intradermal PRRS virus vaccination in swine has been investigated, the high variability between different virus isolates makes it advisable to assess the intradermal response for each vaccine strain.
The MLV vaccine UNISTRAIN® PRRS has recently obtained the indication for intradermal administration with Hipradermic®, a needle-free injector with connectivity developed by HIPRA for the intradermal vaccination of pigs. A study was conducted in 2-week old piglets in order to demonstrate the clinical protection and the duration of immunity after a heterologous challenge provided by the intradermal administration of UNISTRAIN® PRRS in swine with Hipradermic®.
Thirty-seven 2-week-old piglets, clinically healthy and free from virus and antibodies against PRRS, were randomly assigned to three different groups: ID vaccinated group (n=11), intramuscularly (IM) vaccinated group (n=12) and control group (CTR; n=14). Animals in the ID group were immunised intradermally with UNISTRAIN® PRRS vaccine (0.2 ml/dose; 103.5 CCID50/animal) administered with Hipradermic®. Animals in the IM group were immunised intramuscularly with UNISTRAIN® PRRS vaccine (2 ml/dose; 103.5 CCID50/animal; administered with needle and syringe). The animals in the CTR group received 2 ml of PBS using the same strategy as in the IM group. At 26 weeks of age, all piglets were challenged by the intranasal route with a heterologous pathogenic strain of European genotype I of the PRRSV (89% ORF5 homology; 106.39 CCID50/animal). Animals were examined daily after challenge over the following 35 days. Virus detection was performed by real time RT-qPCR (at 2, 5, 8, 14, 21, 28 and 35 days post-challenge) and the Area Under the Curve (AUC) of viraemia was calculated from the challenge to the end of the study. AUC and length of viraemia were analysed using a non-parametric Mann-Whitney U test (p<0.05) and the percentage of viraemic animals using a two-tailed chi-square test/Fisher’s exact test (p<0.05).
The vaccinated groups had a significantly lower serum viral load, as determined by AUC (IM=0.0×100 CCID50/ml; ID=0.0×100 CCID50/ml), when compared to non-vaccinated pigs (CTR=3.1×104 CCID50/ml). In the vaccinated groups, a significant reduction in the number of viraemic animals was observed at: 5, 8, 14, 21, 28 and 35 days after challenge.

  

The length of the viraemia after challenge was also statistically lower in the vaccinated groups compared to non-vaccinated pigs.

  

The results obtained allow us to conclude that the duration of immunity of the UNISTRAIN® PRRS vaccine was achieved 24 weeks after vaccination. In addition, UNISTRAIN® PRRS administered in piglets by the intradermal route with Hipradermic® had a comparable effect on the fast clearance of the virus to IM administration using a traditional syringe and needle. UNISTRAIN® PRRS vaccine administered ID or IM appears to be a useful tool to decrease viraemia and thus achieve a reduction in the infection pressure of the PRRS virus in swine.

UNISTRAIN® PRRS publications, ISERPD 2015

  
Heterologous cell-mediated immune responses against PRRS virus in gilts vaccinated intramuscularly and intradermally with UNISTRAIN® PRRS

Miranda, J. et al.; ISERPD 2015.
As expected, the variability of IFN-γ-SC responses observed among different strains was not related to the percentage of ORF5 similarity with the vaccine strain. Results demonstrated that the ID administration of UNISTRAIN® PRRS confers higher levels of cell-mediated immune response than using the IM route. This phenomenon suggests that ID route could be considered a candidate to develop future PRRS vaccines.

Safety of the intradermal administration of a PRRS vaccine in a swine multicentre field trial

  

The intradermal vaccination of a live PRRS vaccine (UNISTRAIN® PRRS), through the new needle-free injector Hipradermic®, is safe when administered in swine according to the recommended vaccination program.
Current knowledge on PRRS virus immunology is still limited but it seems clear that modified live PRRS vaccines (MLV) are a reasonable choice for the immunization of pigs. Recently, interest in intradermal vaccination in swine has increased due to research into skin and subcutaneous tissue immunology and the possibility of using needle-free injection devices (NFIDs). The use of NFIDs in the swine industry offers some advantages over conventional needle-and-syringe methods, especially due to the reduced pain and stress to pigs and the increase in the uniformity of the dosage administered to the herd.
The MLV vaccine UNISTRAIN® PRRS has recently obtained the indication for intradermal administration with Hipradermic®, a needle-free injector with connectivity developed by HIPRA for the intradermal vaccination of pigs. A multicentre field trial was conducted under field conditions in order to demonstrate the safety of the intradermal administration of UNISTRAIN® PRRS in swine with Hipradermic® .  
A multicentre, randomized, double-blind, controlled trial was carried out in 1532 animals (piglets from 3-4 weeks of age) distributed over 3 commercial farms (farms 1, 2 and 3) in Spain. The animals on each farm were randomly divided into two treatment groups. Group A (n=693) was vaccinated once at 3-4 weeks of age (day 0; d0) with 0.2 ml of UNISTRAIN® PRRS vaccine (103.5 CCID50/animal; strain) administered intradermally with Hipradermic®. Group B, (n=839) as a control group, was injected with 0.2 ml of PBS (phosphate buffered saline) also ID with the same device. All animals included in the trial were individually identified. The pooled results of the three farms were obtained.
Schedule of tasks performed:

  

These parameters were recorded for all the animals included in group A and compared with group B, to assess the safety of the UNISTRAIN® PRRS vaccine administrated intradermally.

No serious or unexpected adverse events attributable to intradermal vaccination with UNISTRAIN® PRRS were observed. Likewise, no post-vaccination general clinical signs attributable to vaccination with UNISTRAIN® PRRS vaccine were observed. No significant differences were observed between the groups in the increase in body temperature after vaccination.
Increase in rectal temperature after vaccination (ºC):  

  

 Regarding local reactions observed after vaccination, slight to moderate inflammation could be seen in group A, which resolved within 2 days post-vaccination. Redness was also observed at the inflammation area in some animals. No nodules were observed in any of the animals on any of the monitoring days. In all cases, reactions resolved spontaneously three days post-vaccination without treatment.
Local reactions observed after vaccination:
  
The results obtained allow us to conclude that vaccination with UNISTRAIN® PRRS vaccine is safe when administered to piglets by the intradermal route with Hipradermic® according to the recommended vaccination program.

How is PRRS transmitted in pigs?

Transmission of PRRS in pigs within herds can be classified as direct, when it is transmitted by direct contact from infected animals to others, and indirect transmission when it is transmitted through fomites or vectors. Regarding direct transmission, we can differentiate between vertical transmission, from sows to their offspring, and horizontal transmission, from infected pigs to their mates.
PRRS in pigs can be transmitted from infected to susceptible pigs through different routes:

Transmission of PRRS in pigs within herds can be classified as direct, when it is transmitted by direct contact from infected animals to others, and indirect transmission when it is transmitted through fomites or vectors. Regarding direct transmission, we can differentiate between vertical transmission, from sows to their offspring, and horizontal transmission, from infected pigs to their mates.
PRRS in pigs can be transmitted from infected to susceptible pigs through different routes:

The main route is direct transmission when infected pigs are in contact with others on the same farm, or in the same barn or pen. To evaluate direct transmission between pigs on the farm we should consider the different routes of virus shedding and its duration. So, PRRS virus can be shed for a long time through multiple routes: nasal secretions, saliva or semen and also, although less frequently, through milk, colostrum, urine or feces. Taking into account all these routes of shedding, we can establish different routes of exposure for the susceptible pigs: oronasal, sexual or percutaneous.
Besides this direct horizontal transmission, vertical transmission can also occur when the PRRS virus crosses the placental barrier during the last trimester of gestation and it can replicate in the endometrial and placental tissues. So, vertical transmission from pregnant sows to their piglets is a very important factor for the circulation of PRRS in pigs.
Indirect transmission is also possible. As we explained in the previous post, Transmission between herds, different vectors and contaminated fomites can spread the PRRS virus on the farm and to other farms as well. In addition, airborne transmission is possible between different pens or barns, or through slurry. It should be borne in mind that the PRRS virus can survive for days in favorable conditions such as organic material, high humidity and low temperatures.
In order to control the transmission not just of PRRS in pigs, but also other secondary bacterial pathogens, different standardized management protocols have been established amongst which Mc Rebel procedures (Management Changes to Reduce Exposure to Bacteria to Eliminate Losses) are the most popular. Basically, rules applied are focused on decreasing contact between potentially susceptible pigs and potentially infected pigs (i.e: all-in-all-out, isolation of sick animals, avoiding or minimizing cross fostering…..)
Finally vaccination cannot develop 100% protection against any infection,  but the vaccination of breeders and piglets can confer a higher immunity status to the herd, decreasing the shedding of PRRS virus from infected animals and increasing the potential infective dose of susceptible pigs. So, UNISTRAIN® PRRS, a live-attenuated PRRS vaccine, VP-046 BIS strain, can be a useful tool for the control and stabilization of PRRS in pigs. UNISTRAIN® PRRS can be used both in breeders and piglets and has demonstrated heterologous protection against different highly pathogenic strains of both genotype I and genotype II.