Antigenic differences among Newcastle disease virus strains of different genotypes used in vaccine formulation affect viral shedding after a virulent challenge☆
Introduction
Newcastle disease virus (NDV), also known as avian Paramyxovirus type-1 virus, is a member of the genus Avulavirus[1] in the Paramyxoviridae family. It is a single stranded, non-segmented, enveloped RNA virus with negative polarity [2]. NDV is composed of six genes and their corresponding six structural proteins: nucleoprotein (NP), phosphoprotein (P), matrix (M), fusion (F), hemagglutinin-neuraminidase (HN), and the RNA polymerase (L). RNA editing of the P protein produces two additional proteins, V and W. The HN and F are glycoproteins that allow binding and fusion of the virus to the host cells to initiate a NDV infection. Antibodies to HN and F are neutralizing and represent the primary protective component induced by Newcastle Disease (ND) vaccines [3].
Antigenic [4] and genetic diversity [5] are recognized within the APMV-1 serotype. At least six distinct lineages of NDV have been identified based on restriction enzyme analysis and nucleotide sequence of the fusion protein gene [5], [6]. Another classification system using full-length sequence to relate the viruses isolated over time has been reviewed by Lomniczi and coworkers [7] and shows two major divisions represented by Class I and Class II, with Class II being further divided into at least eight genotypes. This paper will refer to the second classification system when discussing the ND viruses used. The amino acid diversity across NDV sequences available on GenBank® for both the HN and the F genes displays on average a 10% difference between the genotypes of Class II and a 15% difference between Class I and Class II viruses. Amino acid diversity among strains may have been the basis of the report in 1951 that certain NDV strains were antigenically superior to others when used to formulate a killed vaccine [8].
Historically, NDV isolates have been divided into three groups used to describe their virulence in poultry: lentogen (low virulence), mesogen (moderate virulence) and velogen (high virulence) [2]. Select lentogenic strains are universally used as live vaccines in the commercial poultry industry. Experimental infections of specific pathogen-free (SPF) chickens with these lentogenic vaccine strains cause little to no clinical disease. When these viruses are used in the field they can cause decreased productivity in commercial chickens by inducing a mild respiratory disease, particularly when the birds are infected with other respiratory pathogens or in combination with environmental stressors. Virulent NDV isolates, the cause of ND—called exotic Newcastle disease (END) in the United States (U.S.), are not endemic in the U.S. and can spread rapidly leading to high mortality rates [9]. Symptoms of a virulent NDV infection in susceptible birds may include depression, respiratory distress, hemorrhage in multiple organs, neurological signs and acute death. ND vaccines are widely administered to reduce clinical disease from endemic infections with low virulence strains and can provide protection against disease but not infection with virulent outbreak viruses. Consequently, the primary control measure in the U.S. if an ND outbreak occurs is depopulation of infected or likely exposed animals. This can create a significant financial burden, for example the estimated cost for controlling the California 2002–2003 outbreak exceeded $200 million [10].
In the U.S., and in many countries worldwide, ND prevention is focused on bio-security and the vaccination of poultry with both live and inactivated ND vaccines. Ideally vaccines are administered after maternal antibodies have waned which allows the induction of a good immunological response before the birds are likely to be exposed to a virulent strain of NDV, but because of differences in flock immunity, vaccination is rarely ideally implemented. Both live and inactivated vaccines have their advantages and disadvantages, which have been reviewed previously [11]. Today the strains of NDV used to produce ND vaccines in the U.S., such as LaSota and B1, are phylogenetically in the same genotype as viruses isolated in the 1940s, but are phylogenetically divergent from strains causing the recent outbreaks of ND in North America since the 1970s, such as Fontana/1972, Turkey North Dakota/1992, and California/2002 (see Fig. 1). It is widely recognized that because ND isolates are of one serotype, ND vaccines prepared with any ND lineage, given correctly, can protect poultry from clinical disease and mortality from a virulent ND virus challenge [12], [13], [14]. However, even as far back as 1953 the feasibility of one NDV vaccine being able to protect birds from ND without evaluating the factors for each individual outbreak has been questioned [15]. In 1972, Spalatin and Hanson noted that the new forms of NDV being isolated in the U.S. are able to infect vaccinated chickens and that these new viruses seem partially resistant to the antibodies induced by the current vaccines [16]. More recently, Kapczynski and King showed that current vaccination programs in commercial broilers in the U.S. are not completely effective at preventing clinical disease and virus shedding after experimental challenge with a recent virulent strain [10]. These results along with the susceptibility of vaccinated commercial layers to virulent NDV infection in the California 2002 outbreak suggests the current vaccination programs may not be optimized. The objective of this study was to compare the protection induced by ND vaccines prepared with viruses of five different NDV genotypes by assessing viral shed from vaccinates in addition to the standard observation of morbidity and mortality after challenge. The comparison was done with inactivated vaccines, the only feasible option to utilize the virulent CA 2002 NDV as both a vaccine antigen and a challenge virus. We found that vaccinating with a NDV homologous with the ND challenge virus induced high hemagglutination-inhibiting antibody titers and significantly reduced the amount of virus shed in oral secretions compared to the heterologous vaccines. Vaccines with the ability to reduce viral shed would enhance the role of vaccination in ND control.
Section snippets
Eggs and chickens
Four-week-old, SPF White Leghorn (WL), chickens obtained from the Southeast Poultry Research Laboratory (SEPRL) flocks were separated into six vaccination groups of 16 birds each. The chickens were wing banded and kept in Horsfall isolation units in BSL 3 Ag facilities and allowed to acclimate for 2 days prior to their being vaccinated. Additional birds from this group were bled and tested by hemagglutination inhibition (HI) assay and ELISA (IDEXX, Westbrook, ME) to confirm that the flock was
Results
The five viruses chosen to be used as vaccines differed phylogenetically (Fig. 1, Table 1) and antigenically (Table 2). In evaluating the deduced similarity for the HN and F proteins between the CA02 challenge strain and the vaccine strains, Pigeon84 and Alaska196 are respectively the most and least genetically similar (Table 2). When using a panel of nine different monoclonal antibodies, each virus had a different antigenic pattern of reactivity compared to the CA02 virus antigenic pattern
Discussion
The goal of this study was to determine if the antigenic distance of the vaccine strain, as described by phylogeny, can influence the amount of virus shed after infection with a virulent strain of NDV and thus impact decisions on vaccine formulation and challenge virus for potency testing. We identified four NDV isolates that represented four genotypes different from the CA02 outbreak strain to use in this study as vaccines that have different degrees of amino acid similarity to the CA02 HN and
Acknowledgments
The authors would like to thank Tim Olivier, Suzanne DeBlois, and Dawn Williams-Coplin for their excellent technical assistance, and Roger Brock for animal care assistance. We extend our appreciation to Dr. Mia Kim for her assistance with the animal studies. USDA, ARS CRIS project 6612-32000-049, supported this research.
References (52)
- et al.
The avian response to Newcastle disease virus
Dev Comp Immunol
(2000) - et al.
Third genome size category of avian paramyxovirus serotype 1 (Newcastle disease virus) and evolutionary implications
Virus Res
(2006) - et al.
Protection of chickens against overt clinical disease and determination of viral shedding following vaccination with commercially available Newcastle disease virus vaccines upon challenge with highly virulent virus from the California 2002 exotic Newcastle disease outbreak
Vaccine
(2005) - et al.
Principles of selective inactivation of viral genome. VIII. The influence of beta-propiolactone on immunogenic and protective activities of influenza virus
Vaccine
(1993) - et al.
A recombinant fowlpox virus expressing the hemagglutinin-neuraminidase gene of Newcastle disease virus (NDV) protects chickens against challenge by NDV
Virology
(1990) - et al.
A fowlpox virus vaccine vector with insertion sites in the terminal repeats: demonstration of its efficacy using the fusion gene of Newcastle disease virus
Vet Microbiol
(1990) - et al.
Improved protection from velogenic Newcastle disease virus challenge following multiple immunizations with plasmid DNA encoding for F and HN genes
Vet Immunol Immunopathol
(2005) - et al.
Protective immunity against avian influenza induced by a fowlpox virus recombinant
Vaccine
(1988) - et al.
Protection against diverse highly pathogenic H5 avian influenza viruses in chickens immunized with a recombinant fowlpox vaccine containing an H5 avian influenza hemagglutinin gene insert
Vaccine
(2000) - et al.
Molecular evolution of the Newcastle disease virus matrix protein gene and phylogenetic relationships among the paramyxoviridae
Virus Res
(2000)
Newcastle disease virus evolution. II. Lack of gene recombination in generating virulent and avirulent strains
Virology
A summary of taxonomic changes recently approved by ICTV
Arch Virol
Newcastle disease, other avian paramyxoviruses, and pneumovirus infections
Newcastle disease outbreaks in domestic fowl and turkeys in Great Britain during 1997
Vet Rec
A molecular epidemiological study of avian paramyxovirus type 1 (Newcastle disease virus) isolates by phylogenetic analysis of a partial nucleotide sequence of the fusion protein gene
Avian Pathol
Identification and grouping of Newcastle disease virus strains by restriction site analysis of a region from the F gene
Arch Virol
Comparisons of immunogenicity of five strains of Newcastle disease virus as formalinized vaccines
Vet Med
Control of Newcastle disease by vaccination
Dev Biol (Basel)
Protection of chickens afforded by commercial lentogenic vaccines against challenge exposure to velogenic Newcastle disease virus
Avian Dis
Efficacy of a commercial Newcastle vaccine against velogenic viscerotropic Newcastle disease virus
Avian Dis
Comparative efficacy of the B-1 and VG/GA vaccine strains against velogenic viscerotropic Newcastle disease virus in chickens
Avian Dis
Antigenic differences among strains of Newcastle disease virus
Proc Soc Exp Biol Med
Comparison of B1 and Ulster strains of Newcastle disease virus as vaccines against the viscerotropic form of disease
Avian paramyxovirus type 1 from pigeons: isolate characterization and pathogenicity after chicken or embryo passage of selected isolates
Avian Dis
Characterization of Class I Newcastle disease virus isolates from Hong Kong bird markets and detection using real-time reverse transcription PCR
J Clin Microbiol
Cited by (257)
Efficacy of Newcastle disease LaSota vaccine-induced hemagglutination inhibition antibodies against challenges with heterologous virulent strains of genotypes VII and IX
2023, Veterinary Immunology and Immunopathology
- ☆
Proprietary or brand names used are necessary to report factually on available data. However, the USDA neither guarantees nor warrants the standard of the product, and the use of names by the USDA implies no approval of the product to the exclusion of others that may also be suitable.