Commercial Modified-live Virus Vaccines Research Articles

Transition from one commercial porcine reproductive and respiratory syndrome modified-live virus vaccine to another in a breeding herd and impact on productivity

Porcine reproductive and respiratory syndrome (PRRS) continues to represent a significant cost to the swine industry and efforts are focused on prevention and mitigation of losses across production phases. Herein describes a PRRS modified-live virus (MLV) vaccinated breeding herd that changed commercial MLV vaccines to improve post-weaning performance. Two whole-herd vaccinations with a new PRRS MLV vaccine, administered 4 weeks apart, occurred without breeding herd production disruptions and with limited changes in diagnostic results. Replacement gilts tested PRRS virus negative 10 weeks post vaccination with the new MLV vaccine. Diagnostics were intermittently positive in the breeding herd and early nursery.

Genomic similarity and antibody-dependent enhancement of immune serum potentially affect the protective efficacy of commercial MLV vaccines against NADC30-like PRRSV

Porcine reproductive and respiratory syndrome (PRRS) is one of the most significant diseases affecting the pig industry worldwide. The PRRSV mutation rate is the highest among the RNA viruses. To date, NADC30-like PRRSV and highly pathogenic PRRSV (HP-PRRSV) are the dominant epidemic strains in China; however, commercial vaccines do not always provide sufficient cross-protection, and the reasons for insufficient protection are unclear. This study isolated a wild-type NADC30-like PRRSV, SX-YL1806, from Shaanxi Province. Vaccination challenge experiments in piglets showed that commercial modified live virus (MLV) vaccines provided good protection against HP-PRRSV. However, it could not provide sufficient protection against the novel strain SX-YL1806. To explore the reasons for this phenomenon, we compared the genomic homology between the MLV strain and HP-PRRSV or NADC30-like PRRSV and found that the MLV strain had a lower genome similarity with NADC30-like PRRSV. Serum neutralization assay showed that MLV-immune serum slightly promoted the homologous HP-PRRSV replication and significantly promoted the heterologous NADC30-like PRRSV strain replication in vitro, suggesting that antibody-dependent enhancement (ADE) might also play a role in decreasing MLV protective efficacy. These findings expand our understanding of the potential factors affecting the protective effect of PRRSV MLV vaccines against the NADC30-like strains.

Efficacy evaluation of two commercial modified-live virus vaccines against a novel recombinant type 2 porcine reproductive and respiratory syndrome virus

NADC30-like porcine reproductive and respiratory syndrome virus (PRRSV) causing clinical disease outbreaks has been recently reported in China. The recombination occurring among PRRSV strains could lead to the emergence of novel and more virulent viruses. In our previous study, a novel recombinant type 2 PRRSV (TJnh1501) between NADC30-like and modified-live virus (MLV)-like derived from the Chinese highly pathogenic PRRSV was shown to have higher pathogenicity than NADC30-like PRRSV. It remains unknown whether the emergence of the novel recombinant PRRSV strain can lead to variable protection efficacy of the MLV vaccines. In this paper, two typical commercial MLV vaccines were used to evaluate their efficacy to block TJnh1501 infection and onset of clinical symptoms. Our results showed that both MLV vaccines could shorten the period of fever and reduce viral loads in sera, but were not able to reduce the clinical signs and lung lesions indicating that the two commercial MLV vaccines provide limited cross-protection efficacy against the novel recombinant type 2 PRRSV infection. This study gives valuable suggestions for the use of MLV vaccines to control PRRSV infection in the field.

Efficacy evaluation of three modified-live virus vaccines against a strain of porcine reproductive and respiratory syndrome virus NADC30-like

Porcine reproductive and respiratory syndrome reproductive virus is a devastating pathogen causing tremendous economic losses to swine production worldwide. Emergence of novel and variant PRRSV strains always leads to variable protection efficacy of modified-live virus (MLV) vaccines. Prevalence of PRRSV NADC30-like recently emerging in China has brought about clinical outbreaks of the disease. In the present study, the pathogenicity of a NADC30-like strain CHsx1401 for piglets was analyzed, and the potential cross-protective efficacy of three MLV vaccines including two commercial MLV vaccines and an attenuated low pathogenic PRRSV against this virus was further evaluated in piglets. The NADC30-like CHsx1401 was shown to cause fever, respiratory clinical signs, and lung gross and microscopic lesions of the inoculated piglets, suggesting that this virus is moderate virulent for piglets. Vaccination of piglets with the MLV vaccines could not reduce the clinical signs and lung lesions, and was partially efficacious in the reduction of viral loads in sera upon NADC30-like CHsx1401 challenge, indicating that these three MLV vaccines provide extremely limited cross-protection efficacy against the NADC30-like virus infection. Additionally, Ingelvac PRRS MLV appeared to exert some beneficial efficiency in shortening the period of clinical fever and in improving the growth performance of the challenged pigs. Our findings give valuable guidance for the choice and use of PRRSV MLV vaccines to control NADC30-like virus infection in the field.

Preparation for emergence of an Eastern European porcine reproductive and respiratory syndrome virus (PRRSV) strain in Western Europe: Immunization with modified live virus vaccines or a field strain confers partial protection

The porcine reproductive and respiratory syndrome virus (PRRSV) causes huge economic losses for the swine industry worldwide. In the past several years, highly pathogenic strains that lead to even greater losses have emerged. For the Western European swine industry, one threat is the possible introduction of Eastern European PRRSV strains (example Lena genotype 1.3) which were shown to be more virulent than common Western resident strains under experimental conditions. To prepare for the possible emergence of this strain in Western Europe, we immunized piglets with a Western European PRRSV field strain (Finistere: Fini, genotype 1.1), a new genotype 1 commercial modified live virus (MLV) vaccine (MLV1) or a genotype 2 commercial MLV vaccine (MLV2) to evaluate and compare the level of protection that these strains conferred upon challenge with the Lena strain 4 weeks later. Results show that immunization with Fini, MLV1 or MLV2 strains shortened the Lena-induced hyperthermia. In the Fini group, a positive effect was also demonstrated in growth performance. The level of Lena viremia was reduced for all immunized groups (significantly so for Fini and MLV2). This reduction in Lena viremia was correlated with the level of Lena-specific IFNγ-secreting cells. In conclusion, we showed that a commercial MLV vaccine of genotype 1 or 2, as well as a field strain of genotype 1.1 may provide partial clinical and virological protection upon challenge with the Lena strain. The cross-protection induced by these immunizing strains was not related with the level of genetic similarity to the Lena strain. The slightly higher level of protection established with the field strain is attributed to a better cell-mediated immune response.

Priming Cross-Protective Bovine Viral Diarrhea Virus-Specific Immunity Using Live-Vectored Mosaic Antigens.

Bovine viral diarrhea virus (BVDV) plays a key role in bovine respiratory disease complex, which can lead to pneumonia, diarrhea and death of calves. Current vaccines are not very effective due, in part, to immunosuppressive traits and failure to induce broad protection. There are diverse BVDV strains and thus, current vaccines contain representative genotype 1 and 2 viruses (BVDV-1 & 2) to broaden coverage. BVDV modified live virus (MLV) vaccines are superior to killed virus vaccines, but they are susceptible to neutralization and complement-mediated destruction triggered by passively acquired antibodies, thus limiting their efficacy. We generated three novel mosaic polypeptide chimeras, designated NproE2123; NS231; and NS232, which incorporate protective determinants that are highly conserved among BVDV-1a, 1b, and BVDV-2 genotypes. In addition, strain-specific protective antigens from disparate BVDV strains were included to broaden coverage. We confirmed that adenovirus constructs expressing these antigens were strongly recognized by monoclonal antibodies, polyclonal sera, and IFN-γ-secreting T cells generated against diverse BVDV strains. In a proof-of-concept efficacy study, the multi-antigen proto-type vaccine induced higher, but not significantly different, IFN-γ spot forming cells and T-cell proliferation compared to a commercial MLV vaccine. In regards to the humoral response, the prototype vaccine induced higher BVDV-1 specific neutralizing antibody titers, whereas the MLV vaccine induced higher BVDV-2 specific neutralizing antibody titers. Following BVDV type 2a (1373) challenge, calves immunized with the proto-type or the MLV vaccine had lower clinical scores compared to naïve controls. These results support the hypothesis that a broadly protective subunit vaccine can be generated using mosaic polypeptides that incorporate rationally selected and validated protective determinants from diverse BVDV strains. Furthermore, regarding biosafety of using a live vector in cattle, we showed that recombinant human adenovirus-5 was cleared within one week following intradermal inoculation.

Priming protective BVDV-specific immunity using multi-component mosaic antigens (VAC7P.980)

Abstract Bovine viral diarrhea virus (BVDV), a Flavivirus, plays a key role in bovine respiratory disease complex, which leads to pneumonia and death of calves. Current vaccines are not very effective due, in part, to immunosuppressive traits of the virus. There are diverse BVDV strains and thus, current vaccines contain type 1 and 2 viruses (BVDV-1 & 2). Modified live virus (MLV) vaccines are superior to killed virus, but they are susceptible to antibody neutralization and complement-mediated destruction that limits their efficacy in neonates. We generated three novel mosaic polypeptide chimeras, designated NproE2123; NS231; and NS232, which represent determinants conserved among BVDV strains and these antigens are the main targets involved in protection. We confirmed that a proto-type adenovirus-vectored vaccine expressing these antigens was recognized by mAbs, sera, and T cells raised against diverse BVDV strains. In a poof-of-concept efficacy study, the vaccine induced significantly higher IFN-γ spot forming cells (p<0.05), T cell proliferation (p<0.05), and SN titers (p<0.05) against BVDV-1 & 2 as compared to immune responses induced by a commercial MLV vaccine. Following challenge, the calves immunized with the proto-type and the MLV vaccines had mild clinical scores compared to naïve controls. These results support the hypothesis that a broadly protective subunit vaccine can be generated using mosaic polypeptides that incorporate protective motifs from diverse BVDV strains.

A PCR-based screening program to assess the prevalence of Taylorella equigenitalis in breeding stallions in South Africa

spread via respiratory route through animal movements to seven other premises (identified after an extensive serosurveillance investigation of epidemiologically linked facilities). The aim of the present study was to assess the long-term consequences of this series of disease events on the equine industry and the current EAV status of Argentina. A total of 38 stallions (belonging to the “Silla Argentina” breed) became seropositive during this occurrence. Twenty-nine were castrated without additional testing to determine whether any of them were EAV carriers and semen shedders. Semen samples for virological determination were obtained from the remaining nine stallions, and EAV was isolated from 4 of them. Sequencing and phylogenetic analysis of ORF5 of each isolate confirmed that they were identical to each other and to isolates from the cases of abortion and foal death, as well as virus isolated from the imported frozen semen. All clustered within the European subgroup 1 lineage of EAV. Three of the four EAV shedding stallions were castrated; one remains intact but is not allowed to be used for breeding because of legal restrictions imposed by the owner. A program of nonmandatory vaccination against equine viral arteritis (EVA) in stallions of different breeds was instituted; 317 stallions were vaccinated with a commercial modified-live virus vaccine (ARVAC , Pfizer Animal Health) in 2010 and with an inactivated virus vaccine (Artervac , Pfizer Animal Health) in 2011. All of the vaccinated stallions must be revaccinated every 6 months, or tested for EAV in semen before each breeding season because of their seropositive status. Seroepidemiological surveillance performed after the outbreak revealed 46 out of 2805 (August to December 2010), 320 out of 7618 (2011) and 29 out of 2087 (January to April 2012) samples were positive. Based on their respective histories, seropositive horses had either been previously vaccinated against EVA, or were animals involved in the series of outbreaks of EVA in 2010. No new seropositive horses were found since August 2010. The reintroduction of EAV in 2010 has had significant economic consequences for the Argentinean horse industry, including establishment of the carrier state in highly valuable stallions and the need for implementation of vaccination against the disease.

PORCINE RESPIRATORY AND REPRODUCTIVE SYNDROME VIRUS VACCINOLOGY: A REVIEW FOR COMMERCIAL VACCINES

Porcine Reproductive and Respiratory Syndrome (PRRS) since its appearance in Europe in the early 1990’s has resulted in tremendous economic losses. Under field conditions vaccination is one of the most efficient strategies for the prevention and control of PRRS. The aim of this study is to perform the PRRSV vaccinology regarding current status of commercial vaccines in Europe. There are two types of PRRSV commercial available vaccines in Europe: Killed Virus (KV) or inactivated vaccines and Modified-Live Virus (MLV) or attenuated vaccines. EU KV commercial vaccines provide limited efficacy due to the weak stimulation of the immune system and no effective induction of neutralizing antibodies. However, KV vaccines can induce a strong Cell Mediated Immune (CMI) response. One the other hand, commercial EU MLV vaccines provide effective strain-specific protection, only partial protection against genetically heterologous PRRSV and elicit relatively late humoral and CMI responses which lead to delayed protection. In Europe, the KV vaccination prove to reduce the negative effects of PRRSV in breeding herds, improving their reproductive performance, e.g., increase of farrowing rate and number of live or weaned pigs, reduction of premature farrowing rate, abortion rate and number of mummified and stillborn piglets. The use of commercial MLV vaccines in PRRSV-infected breeding herds leads to improvement of: (a) reproductive performance e.g., reduction of the abortion and return to oestrus rate and increase of the farrowing rate and number of weaners, ( b) the viraemic status, morbidity and mortality rate of piglets and (c) the growth performance of vaccinated pigs. In conclusion, nowadays the use of MLV or KV vaccines in Europe is the most economical tool to control the economic losses of PRRSV infection. However, the development of more efficacious PRRSV vaccines is the significant future goal for PRRSV vaccinology.

Evaluation of the safety of vaccinating mares against equine viral arteritis during mid or late gestation or during the immediate postpartum period

To determine whether it is safe to vaccinate pregnant or postpartum mares with a commercial modified-live virus vaccine against equine viral arteritis (EVA). Design-Randomized controlled study. Animals-73 mares and their foals. Mares were vaccinated during mid gestation, during late gestation, or 2 or 3 days after parturition with a commercial modified-live virus vaccine or were not vaccinated. Foaling outcomes were recorded, and serum, blood, milk, and nasopharyngeal samples were obtained. All mares vaccinated during mid gestation foaled without any problems; 21 of 22 mares in this group had antibody titers against EAV at the time of foaling. Of the 19 mares vaccinated during late gestation, 3 aborted; antibody titers against EAV were detected in 13 of 15 mares from which serum was obtained at the time of foaling. All postparturient vaccinates were seronegative at foaling; all of them seroconverted after vaccination. No adverse effects were detected in any of their foals. When faced with a substantial risk of natural exposure to EAV, it would appear to be safe to vaccinate healthy pregnant mares up to 3 months before foaling and during the immediate postpartum period. Vaccinating mares during the last 2 months of gestation was associated with a risk of abortion; this risk must be weighed against the much greater risk of widespread abortions in unprotected populations of pregnant mares naturally infected with EAV.