Elsevier

Vaccine

Volume 25, Issue 41, 10 October 2007, Pages 7238-7246
Vaccine

Antigenic differences among Newcastle disease virus strains of different genotypes used in vaccine formulation affect viral shedding after a virulent challenge

https://doi.org/10.1016/j.vaccine.2007.07.017Get rights and content

Abstract

Strains of Newcastle disease virus (NDV) can be separated into genotypes based on genome differences even though they are antigenically considered to be of a single serotype. It is widely recognized that an efficacious Newcastle disease (ND) vaccine made with any NDV does induce protection against morbidity and mortality from a virulent NDV challenge. However, those ND vaccines do not protect vaccinates from infection and viral shed from such a challenge. Vaccines prepared from ND viruses corresponding to five different genotypes were compared to determine if the phylogenetic distance between vaccine and challenge strain influences the protection induced and the amount of challenge virus shed. Six groups of 4-week-old specific pathogen-free Leghorn chickens were given oil-adjuvanted vaccines prepared from one of five different inactivated ND viruses including strains B1, Ulster, CA02, Pigeon84, Alaska196, or an allantoic fluid control. Three weeks post-vaccination, serum was analyzed for antibody content using a hemagglutination inhibition assay against each of the vaccine antigens and a commercial NDV ELISA. After challenge with virulent CA02, the birds were examined daily for morbidity and mortality and were monitored at selected intervals for virus shedding. All vaccines except for the control induced greater than 90% protection to clinical disease and mortality. The vaccine homologous with the challenge virus reduced oral shedding significantly more than the heterologous vaccines. NDV vaccines formulated to be phylogenetically closer to potential outbreak viruses may provide better ND control by reducing virus transmission from infected birds.

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.

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