Changes in circulating lymphocytes and lymphoid tissue associated with vaccination of colostrum deprived calves.

The objective of this study was to compare immunological responses and lymphoid depletion in young, colostrum deprived calves following administration of vaccines containing modified-live bovine viral diarrhea virus (BVDV). A group of calves exposed to a typical virulence non-cytopathic (ncp) BVDV-2 field strain (ncp exposed) was included to compare responses of calves receiving vaccine to responses generated against a field strain (mimicking a natural infection). A negative control group administered a placebo was used in all comparisons. All vaccines used in the study were administered per manufacturer recommendations while ncp BVDV exposed calves received 5 ml intranasally (2.5 ml/nare; 4.2 × 106 TCID50/ml) of the BVDV-2 field strain. Samples collected at each time point included nasal swabs for virus detection, blood samples for complete blood counts and detection of viremia, PBMCs for flow cytometric analysis, serum for virus neutralization titers, and thymus tissue at necropsy for evaluation of lymphoid depletion. A measurable neutralizing BVDV titer was observed for all treatment groups excluding the control animals, which remained negative during the study period. Virus shedding was only detected from the ncp vaccinated and ncp exposed calves. A decline from baseline was observed for peripheral lymphocyte and CD4+ cells for the groups receiving the adjuvanted cytopathic (cp) vaccine, the double deleted genetically modified (ddGM) vaccine, the ncp vaccine and ncp exposed calves, but not for the control group or groups receiving cp vaccines. Thymus depletion was observed for the ncp vaccine and ncp exposed calves and to a lesser extent for the ddGM vaccine calves. Collectively, these data suggest that the virus biotype, method of attenuation, presentation, and use of adjuvant will influence vaccine impacts on lymphoid tissues and the immune response. As such, multiple variables should be considered when determining costs and benefits of vaccination.

Gilt Vaccination with a Mixed Administration of a PRRS MLV and a PPV1 Subunit Vaccine Protects against Heterologous PRRSV1 Infection and Prevents Detrimental Effects on Piglet Performance.

The efficacy of the combined administration of a porcine reproductive and respiratory syndrome (PRRS) modified live virus (MLV) vaccine and a porcine parvovirus 1 (PPV1) subunit vaccine in gilts was addressed in two experiments. Experiment A aimed to establish a 4-week onset of immunity (OOI). Gilts were randomly distributed in three treatment groups: non-vaccinated control animals (group 1), animals vaccinated with the combined vaccine (group 2), and a third group that consisted of animals vaccinated with the PRRS MLV vaccine alone (group 3). Four weeks after the first vaccination, gilts were challenged with a heterologous PRRS virus 1 (PRRSV1) and euthanized three weeks after. Besides this, experiment B pursued a 17-week duration of immunity (DOI). In this case, gilts were distributed in the same treatment groups, but for the third group, which consisted of non-vaccinated, non-challenged animals were used instead. For the DOI assessment, gilts were artificially inseminated 4 weeks after the first vaccination, challenged at day 90 of gestation, and followed up, together with their offspring, until day 20 post-farrowing. Serology and viremia post-challenge were determined in gilts from both experiments, while farrowing and piglet performance were only evaluated in experiment B. Overall, the combined vaccine helped to protect gilts from viremia post-challenge and, consequently, to prevent PRRS clinical symptoms and diminish the proportion of piglets infected congenitally or early in life. The combined vaccine also elicited a significant improvement in piglet survival rate and growth performance until weaning. The present results reveal efficacy and lack of interference of the mixed use of the tested vaccines against PRRSV1 infection, with at least 4-week OOI and 17-week DOI.

A novel subunit vaccine based on the viral protein 2 of porcine parvovirus: safety profile in bred pigs at different stages of the reproduction cycle and in offspring.

Porcine parvovirus 1 (PPV1) viral protein (VP) 2 is the primary antigen responsible for inducing specific protective immunity, so it is a desirable target for development of recombinant subunit vaccines to prevent PPV1 disease. The objective of this study was to evaluate repeated doses of a novel VP2-based PPV1 subunit vaccine, namely ReproCyc® ParvoFLEX, for safety in bred pigs and in offspring under experimental settings. Therefore, the investigation of safety at all breeding stages was evaluated in four independent studies involving: pre-breeding gilts (study A), breeding-age gilts and boars (study B), early and late gestating sows and offspring (study C) and lactating sows and offspring (study D). In all four studies, animals were free from PPV1 based on serology and PCR prior to inclusion. All studies comprised one or two vaccinated groups that received the PPV1 subunit vaccine and a negative control group. Thus, safety was established due to the lack of significant differences between the vaccinated groups and the corresponding unvaccinated (negative control) groups. Gilts, sows and boars were evaluated for local and systemic reactions after vaccination as well as for reproductive performance. The survival rate and average daily weight gain (ADWG) from birth to weaning in offspring was evaluated in studies C and D. Additionally, serology was determined in studies A, C and D. The vaccine was shown to be safe with no relevant significant differences between vaccinated and unvaccinated groups in any experiment. Therefore, repeated doses of ReproCyc® ParvoFLEX were safe in target animals at different stages of the reproductive cycle and in offspring, placing this vaccine as a suitable candidate for mass vaccination programs in breeding herds.

Influenza A virus shedding reduction observed at 12 weeks post-vaccination when newborn pigs are administered live-attenuated influenza virus vaccine.

BACKGROUND: Influenza A virus in swine (IAV-S) causes an acute respiratory disease of swine which results in great economic losses. A bivalent H1N1 and H3N2, NS1-truncated live-attenuated IAV-S vaccine (LAIV, Ingelvac Provenza™ ) has recently become available. OBJECTIVE: Reduction of shedding during an outbreak in the nursery or finisher is an important parameter from an epidemiological control strategy; therefore, a laboratory efficacy study was conducted to evaluate nasal virus shedding when vaccinated pigs were challenged with either heterologous H1N2 or H3N2 strains 12 weeks post-vaccination. METHODS: Between 1 and 5 days of age, pigs born to IAV-S seronegative dams were intranasally administered 1 mL of vaccine or saline. At 30 days post-vaccination, pigs were weaned and randomized into two different challenge groups consisting of vaccinated pigs and control pigs commingled within pens for the two challenge groups. At 85 days post-vaccination, pigs in the first group were challenged with A/Swine/North Carolina/001169/2006 H1N2 challenge strain, and the second group was challenged with A/Swine/Nebraska/97901-10/2008 H3N2. Nasal swabs were collected daily for five days and tested by virus isolation. RESULTS AND CONCLUSION: This study showed significant reduction in nasal virus shedding with regard to both frequency and duration. A 1 mL intranasal dose of Ingelvac Provenza™ given as early as 1 day of age showed protection for at least 12 weeks later as evidenced by the reduction of shedding live, viable virus after challenge with either a heterologous H1N2 strain or a heterologous H3N2 strain.

Live attenuated influenza virus vaccine reduces virus shedding of newborn piglets in the presence of maternal antibody.

BACKGROUND: Influenza A virus in swine (IAV-S) causes an acute respiratory disease of swine which results in great economic losses in pig production. Major control strategies include the use of killed vaccines (KV) in breeding females to confer passive immunity to their offspring. A bivalent H1N1 and H3N2 NS1-truncated live attenuated IAV-S vaccine have recently become available, which showed promising results in young pigs. OBJECTIVE: The aim of this study was to investigate the effect of an intranasal vaccination of newborn pigs with or without maternally derived antibodies (MDA) on virus shedding (via nasal swabs tested by virus isolation). METHODS: The study was performed as intratracheal challenge experiments with either a heterologous H1N2 or H3N2 viruses. RESULTS AND CONCLUSION: The results of this study showed a significant decrease in the incidence and duration of shedding viable virus for vaccinated newborn piglets with or without MDA, providing strong evidence that intranasal vaccination is overcoming passively acquired maternal immunity. This study indicates that intranasal vaccination with a truncated NS1 live attenuated IAV-S vaccine of newborn piglets with maternal antibodies can be a valuable tool for reducing the prevalence of heterologous H1N2 and H3N2 IAV-S in pig herds.

Insertion and deletion in a non-essential region of the nonstructural protein 2 (nsp2) of porcine reproductive and respiratory syndrome (PRRS) virus: effects on virulence and immunogenicity.

Developing a vaccine that can differentiate infected and vaccinated animals (DIVA) is a new challenge in the design of a vaccine for porcine reproductive and respiratory syndrome virus (PRRSV). Nonstructural protein 2 (nsp2) is the single largest viral product, and it has multiple roles in polypeptide processing and replication complex formation. Using reverse genetics and an infectious PRRSV cDNA clone, we constructed several deletion mutants in the non-essential region of nsp2. One mutant, which has a 131 amino acid deletion within a relatively conserved region of nsp2, was recovered and found to produce a viable virus. The deleted region was replaced with a peptide tag encoding eight amino acids. A recombinant virus containing the 131 amino acid deletion was found to produce normal virus yields in MARC-145 cells and porcine alveolar macrophages (PAM); however, gross and micro-histopathology showed that the virus was less virulent in pigs. The 131 amino acid peptide was expressed as a recombinant protein and used to coat enzyme-linked immunosorbent assay (ELISA) plates. This peptide was recognized by sera from pigs infected with wild-type virus, but not by sera from pigs infected with the deletion mutant. The results from this study show that nsp2 is an important target for the development of marker vaccines and for virus attenuation.