Department of Veterinary Medicine
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Item Newcastle Disease Virus as a Vaccine Vector for Development of Human and Veterinary Vaccines(MDPI, 2016-07-04) Kim, Shin-Hee; Samal, Siba K.Viral vaccine vectors have shown to be effective in inducing a robust immune response against the vaccine antigen. Newcastle disease virus (NDV), an avian paramyxovirus, is a promising vaccine vector against human and veterinary pathogens. Avirulent NDV strains LaSota and B1 have long track records of safety and efficacy. Therefore, use of these strains as vaccine vectors is highly safe in avian and non-avian species. NDV replicates efficiently in the respiratory track of the host and induces strong local and systemic immune responses against the foreign antigen. As a vaccine vector, NDV can accommodate foreign sequences with a good degree of stability and as a RNA virus, there is limited possibility for recombination with host cell DNA. Using NDV as a vaccine vector in humans offers several advantages over other viral vaccine vectors. NDV is safe in humans due to host range restriction and there is no pre-existing antibody to NDV in the human population. NDV is antigenically distinct from common human pathogens. NDV replicates to high titer in a cell line acceptable for human vaccine development. Therefore, NDV is an attractive vaccine vector for human pathogens for which vaccines are currently not available. NDV is also an attractive vaccine vector for animal pathogens.Item Innovation in Newcastle Disease Virus Vectored Avian Influenza Vaccines(MDPI, 2019-03-26) Kim, Shin-Hee; Samal, Siba K.Highly pathogenic avian influenza (HPAI) and Newcastle disease are economically important avian diseases worldwide. Effective vaccination is critical to control these diseases in poultry. Live attenuated Newcastle disease virus (NDV) vectored vaccines have been developed for bivalent vaccination against HPAI viruses and NDV. These vaccines have been generated by inserting the hemagglutinin (HA) gene of avian influenza virus into NDV genomes. In laboratory settings, several experimental NDV-vectored vaccines have protected specific pathogen-free chickens from mortality, clinical signs, and virus shedding against H5 and H7 HPAI viruses and NDV challenges. NDV-vectored H5 vaccines have been licensed for poultry vaccination in China and Mexico. Recently, an antigenically chimeric NDV vector has been generated to overcome pre-existing immunity to NDV in poultry and to provide early protection of poultry in the field. Prime immunization of one-day-old poults with a chimeric NDV vector followed by boosting with a conventional NDV vector has shown to protect broiler chickens against H5 HPAI viruses and a highly virulent NDV. This novel vaccination approach can provide efficient control of HPAI viruses in the field and facilitate poultry vaccination.Item Development of avian paramyxovirus 3 as a vaccine vector against infectious bursal disease in one-day-old specific pathogen free chickens(2021) Varghese, Berin Parambethu; Zhu, Xiaoping; Veterinary Medical Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)ABSTRACTInfectious bursal disease (IBD) is an acute, highly contagious, immunosuppressive disease affecting young chickens, resulting in substantial economic losses to the poultry industry worldwide. Although strict hygienic measures and various vaccination strategies have been adopted, IBD remains a major problem for the poultry industry. The economic significance of this disease is exhibited in two ways. First, the disease can cause high morbidity and mortality. Second, severe prolonged immunosuppression of chickens when infected at an early age leads to susceptibility to other diseases and vaccination failure. Therefore, chicks should be protected from early infection, usually achieved by vaccinating breeder flocks and active immunization of the newly hatched chicks. Vaccines include live-attenuated, viral vectored recombinant, subunit, and inactivated vaccines currently available to control infectious bursal disease (IBD). The major flaws of available vaccines are the reversion to virulence, the generation of new variant viruses, inability to replicate in the presence of maternal antibodies, lack of proper delivery systems, recombination and integration into the host genome, and inadequate systemic immune response. To overcome these obstacles, we have evaluated avian paramyxoviruses (APMVs) as vaccine vectors to generate vaccines against IBD. In the present study, we constructed recombinant Newcastle disease virus (NDV) strain LaSota (rLaSota/VP2) and recombinant avian paramyxovirus-3 (APMV-3) strain Netherlands expressing VP2 protein (rAPMV-3/VP2), the immunogenic protein of IBDV, and to evaluate their protective efficacies following immunization of one-day-old specific pathogen-free (SPF) chicks. Our results showed that both recombinant viruses stably express the VP2 protein, and their in vitro growth characteristics were almost similar to their respective parental viruses. Immunization of one-day-old SPF chicks demonstrated that rAPMV-3/VP2 protein elicited IBDV specific neutralizing antibodies and provided complete protection against the IBDV STC challenge. In addition, the rAPMV-3/VP2 protects chickens from clinical signs, gross lesions, and histopathology even at lower vaccine doses. Moreover, rAPMV-3/VP2 provides slightly better protection than the commercial vaccine from histopathology lesion against IBD at four weeks of age. This study suggests that recombinant APMV-3 expressing VP2 protein could be used as a potential vaccine against IBD in field conditions where maternal antibodies exist.Item IMPROVED NEWCASTLE DISEASE VIRUS VACCINES AND VECTORS(2017) Manoharan, Vinoth Kumar; Samal, Siba K; Veterinary Medical Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Newcastle disease (ND) is an economically important disease of poultry worldwide. The use of vaccines to control ND is necessary because of frequent outbreaks of the disease in enzootic countries. The fusion (F) and hemagglutinin-neuraminidase (HN) proteins of Newcastle disease virus (NDV) are multifunctional proteins that play critical roles during infection. The F protein of NDV is a type I membrane glycoprotein that mediates the fusion of viral envelope to the host cell membrane. The F protein activation initiates a series of conformational changes in the F protein leading to virus-cell membrane fusion, which occurs at the cell surface at neutral pH thus modulating NDV entry and spread. In the present study, we investigated the role of tyrosine to alanine mutation at amino acid position 524 and 527 in the F protein cytoplasmic tail (CT) of NDV strain LaSota by using reverse genetic techniques. Our results suggest that tyrosine residues at 524 and 527 position of F protein CT domain play a major role in fusogenicity and in replication thus modulating NDV infectivity. The F protein is synthesized as an inactive precursor, F0, which is functionally activated after cleavage by host cell proteases into F1 and F2 polypeptides, linked by disulfide bonds. The amino acid sequence surrounding the F protein cleavage site determines the virulence of NDV. We also studied the role of other avian paramyxovirus fusion protein cleavage site sequences in F protein cleavage of NDV strain Banjarmasin. This study has helped us to understand the requirement of F protein cleavage site in proteolytic processing, plaque formation and virus infectivity. Further, the role of these F cleavage site mutant viruses as genotype-matched vaccines for virulent NDV infection has been explored. Reverse genetics has also been used to develop NDV strains as a potential vaccine vectors for various human and animal pathogens, such as highly pathogenic avian influenza (H5N1), human immunodeficiency virus, severe acute respiratory syndrome coronavirus, ebola virus, respiratory syncytial virus and human parainfluenza virus type 3. NDV has several characteristics that makes it a suitable candidate for vaccine vector development. It is safe in humans and animals due to natural host range restriction, expresses foreign protein abundantly, infects via intranasal route, produces both humoral and mucosal immune responses, is antigenically distinct from human and animal pathogens, and lack of preexisting immunity to NDV in humans and animals. In one vaccine trial with non-human primates, the mesogenic NDV strain Beaudette C (BC) replicated to a high titer and induced a substantially higher antibody response compared to the lentogenic strain LaSota, and thus appeared to be more effective. However, NDV strains that have a polybasic cleavage site in the F protein and an intracerebral pathogenicity index (ICPI) >0.7 have been classified as Select Agents. Most mesogenic strains, including strain BC, fall into this category and therefore cannot be handled in BSL-2 conditions. In this study, we constructed a series of recombinant (rNDV) vectors containing the cleavage site sequence of avirulent strain LaSota and other avian paramyxoviruses, together with various regions of the F protein exchanged between NDV strains AKO-18 and BC. We used these modified rNDV vectors to express SIV gp160 envelope protein and immunized guinea pigs. Our results showed that rNDV/SIV vaccines were immunogenic and effectively neutralized SIV mac251 strain in vitro. These results support the idea of the use of NDV as a vaccine vector for expression of SIV immunogens capable of inducing neutralizing antibodies against diverse SIV strains, thus providing an improved vaccine vector platform for ultimately testing the NDV vectored vaccines in non-human primates and humans.Item IMPROVED INFECTIOUS LARYNGOTRACHEITIS VIRUS VACCINES USING NEWCASTLE DISEASE VIRUS VECTOR(2013) Kanabagatte Basavarajappa, Mallikarjuna; Samal, Siba K; Veterinary Medical Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Infectious laryngotracheitis (ILT) is a highly contagious acute respiratory disease of chickens for which safe and efficacious vaccines are not available currently. In the present study, we have generated three recombinant Newcastle disease viruses (rNDV's) expressing three major envelope glycoproteins gB, gC and gD of ILTV individually. A single oculonasal inoculation of chickens with rNDV's elicited detectable level of systemic antibodies specific to ILTV. Following challenge with virulent strain of ILTV, chickens immunized with the rNDV's displayed partial protection with reduced clinical signs and shorter duration of disease compared to the control group. Our data suggested that NDV vectored ILTV vaccines are useful against ILTV infection, but might require augmentation by a second dose or require modification of ILTV glycoproteins which allow them to incorporate into the mature rNDV virions for better induction of humoral and cell mediated immune responses.Item Sequence analysis of fusion protein gene of Newcastle disease virus isolated from outbreaks in Egypt during 2006(2011-05-18) Mohamed, Mahmoud HA; Kumar, Sachin; Paldurai, Anandan; Samal, Siba KBackground: Newcastle disease virus represents APMV-1 and is the most characterized among all APMV types. The F protein cleavage site sequence is a well-characterized determinant of NDV pathogenicity in chickens. In this study, the sequences of fusion protein (F) gene of three Newcastle disease virus (NDV) strains isolated from outbreak in chickens in the Al-Sharkia province of Egypt in 2006 were determined. Findings: The viral genomic RNAs were extracted from the infective allantoic fluid and F gene is amplified using primer sets designed from the available sequences of NDV strains from GenBank. The pathogenicity of NDV strains was determined by three internationally recognized tests mean death time, intracerebral pathogenicity index, and intravenous pathogenicity index. The phylogenetic analysis showed that the Egypt isolates are closely related with the genotype II of class II NDV strains. Conclusions: The sequences of the F genes of the 2006 Egypt isolates are closely related to that of the 2005 Egypt isolate from the same province suggesting that these strains are probably circulating in the vaccinated bird population in Egypt until development of an outbreak.