Efficacy of a high quality O1/Campos foot-and-mouth disease vaccine upon challenge with a heterologous Korean O Mya98 lineage virus in pigs

In 2010 serotype O foot-and-mouth disease virus of the Mya98 lineage/SEA topotype spread into most East Asian countries. During 2010–2011 it was responsible for major outbreaks in the Republic of Korea where a monovalent O/Manisa vaccine (belonging to the ME-SA topotype) was applied to help control the outbreaks. Subsequently, all susceptible animals were vaccinated every 6 months with a vaccine containing the O/Manisa antigen. Despite vaccination, the disease re-occurred in 2014 and afterwards almost annually. This study focuses on the in vivo efficacy in pigs of a high quality monovalent commercial O₁/Campos vaccine against heterologous challenge with a representative 2015 isolate from the Jincheon Province of the Republic of Korea. Initially, viral characterizations and r₁ determinations were performed on six viruses recovered in that region during 2014–2015, centering on their relationship with the well characterized and widely available O₁/Campos vaccine strain. Genetic and antigenic analysis indicated a close similarity among 2014–2015 Korean isolates and with the previous 2010 virus, with distinct differences with the O₁/Campos strain. Virus neutralisation tests using O₁/Campos cattle and pig post vaccination sera and recent Korean outbreak viruses predicted acceptable cross-protection after a single vaccination, as indicated by r₁ values, and in pigs, by expectancy of protection. In agreement with the in vitro estimates, in vivo challenge with a selected field isolate indicated that O₁/Campos primo vaccinated pigs were protected, resulting in a PD50 value of nearly 10. The results indicated that good quality oil vaccines containing the O₁/Campos strain can successfully be used against isolates belonging to the O Mya98/SEA topotype.     

Antigenic and immunogenic spectrum of foot-and-mouth disease vaccine strain O1 Campos against representative viruses of topotypes that circulated in Asia over the past decade

Identifying vaccine strains to control outbreaks of foot-and-mouth disease virus that could spread to new regions is essential for contingency plans. This is the first report on the antigenic/immunogenic relationships of the South American O1/Campos vaccine strain with representative isolates of the three currently active Asian type O topotypes. Virus neutralization tests using O1/Campos post-vaccination sera derived from cattle and pigs predicted for both species acceptable cross-protection, even after single vaccination, established by r1 values and by expectancy of protection using monovalent or polyvalent vaccines. The results indicate that effective oil vaccines containing the O1/Campos strain can be used against Asian isolates, expanding the scope of O1/Campos strain included in vaccine banks to control emergencies caused by Asian viruses, even on single-dose vaccination, and to cover the need of effective vaccines in Asia during systematic vaccination.     

The field effectiveness of routine and emergency vaccination with an inactivated vaccine against foot and mouth disease

High potency, inactivated foot and mouth disease (FMD) vaccines may be used in non endemic countries for emergency vaccination during outbreaks in order to prevent virus spread. In endemic countries either standard or high potency vaccines are used for routine vaccination. Despite their wide use there is a shortage of data on the field effectiveness of inactivated FMD vaccines. Epidemics of FMD caused by viruses of serotype O occur frequently in Israel, where a high potency (≥6PD₅₀) vaccine is used for both routine and emergency vaccination. We investigated an outbreak of FMD caused by a virus of serotype O, which took place during 2011 in a feedlot and an adjacent dairy herd. Post outbreak testing of antibodies against non-structural protein demonstrated that infection occurred in 96% of the calves that received two doses of vaccine at least three months prior to the outbreak and more than 50% showed clinical signs consistent with FMD. Replacement heifers that had been vaccinated 3–5 times with the last vaccination administered 7 months prior to the outbreak were all infected and 18% showed clinical signs. Testing of cattle sera of the same vaccination status as the affected cattle demonstrated low neutralizing antibody (NA) titers against the field virus strain and an r₁ value of 0.37 compared to the vaccine strain. In contrast, cattle vaccinated only once but up to two weeks before the outbreak, were almost all protected from clinical disease and to a lesser extent, protected from FMD virus infection, despite low NA titers. We conclude that emergency vaccination was highly effective due to a mechanism not associated with NA, whereas routine vaccination with the same vaccine formulation provided only limited protection due to poor longevity of the elicited immunity and low matching with the field strain (despite an r₁ higher than 0.3).     

Protective effects of high-potency FMDV O1 Manisa monovalent vaccine in cattle challenged with FMDV O/SKR/2010 at 7 or 4 days post vaccination

Serotype O foot-and-mouth disease (FMD) virus belonging to the SEA topotype continues to be a significant problem in the Eastern Asia region, with outbreaks in Japan and South Korea resulting in the culling of over 3.5 million cattle and pigs in recent years. High-potency O1 Manisa vaccine was previously shown to provide protection in cattle 21 days post vaccination (dpv) following challenge with a representative virus, O/SKR/2010. This study tested the ability of the O1 Manisa vaccine to protect cattle from infection and disease with the O/SKR/2010 virus within just 4 or 7 days post vaccination. The vaccine protected 50% of cattle from clinical disease when administered 7 days prior to challenge, but was not protective with just 4 days between vaccination and challenge. Viraemia was significantly reduced in animals challenged 7 dpv but not 4 dpv, compared to unvaccinated controls, however, there were no effects on the level of virus detected in nasal and oral secretions regardless of vaccination time. The level of neutralising antibodies detected in cattle challenged 7 dpv correlated with protection from clinical disease. All animals seroconverted to FMDV non-structural proteins, suggesting no sterile protection. An equal number of animals became persistently infected in both vaccine groups. The results indicated that high-potency O1 Manisa vaccine administered just 7 days prior to challenge should provide partial protection of cattle if an outbreak of O/SKR/2010, or related viruses, occurs, and would be useful to limit spread of FMDV when used in conjunction with other control measures.     

Characterization of foot-and-mouth disease virus from outbreaks in Ecuador during 2009-2010 and cross-protection studies with the vaccine strain in use in the region

During the years 2009 and 2010 relevant epidemic waves of foot-and-mouth disease (FMD) serotype O occurred in Ecuador, representing a great drawback for the last stages of the ongoing eradication program in South America. This study describes the molecular and antigenic characterizations of 29 isolates collected from various regions in the country and their relationship to the vaccine strain. The phylogenetic tree derived from sequences spanning the complete VP₁ protein showed that, despite the widespread origin of the viruses, they were all related among themselves and to previous isolates occurring in 2008, with around 10% difference with the vaccine strain O1/Campos. The high level of sequence conservation among different isolates in the various regions of Ecuador pointed to a common origin, suggesting animal movements as possible sources of viral spread. Monoclonal antibody profiling grouped the isolates in two major reactivity patterns which differed from that of the vaccine strain. Both profiles showed loss of reactivity with the same four MAbs, three of them with neutralizing properties. Additional sites were lost in the profile representing most of the 2010s viral samples. Levels of protective antibodies induced by the vaccine against the field strains assessed by in vitro vaccine matching studies also pointed to an increased temporal pattern of loss of a protective response. Moreover, results obtained with in vivo challenge in the protection against podal generalization test in cattle, clearly indicated lack of appropriate protection of the Ecuadorian field strains by the vaccine virus in use, which in the case of a 2010 variant was observed even after revaccination.     

A serological evaluation of 1979-1982 Kenyan foot-and-mouth disease type SAT 2 viruses

Serological evaluations of foot-and-mouth disease type SAT 2 viruses isolated in Kenya between 1979 and 1982 were performed using the two-dimensional microneutralization test. Nine field isolates of epizootiological significance were compared with four vaccine viruses. The results obtained identified Tan 5/68 as the most appropriate reference vaccine virus strain since it had the broadest serological spectrum. Potent Tan 5/68 vaccines would be expected to provide adequate protection against the contemporary SAT 2 field viruses. In the case of K183/74, which also was shown to have a broad spectrum with viruses isolated in Kenya, the results show that the 1982 isolate from central Kenya was significantly divergent (r less than 1.00 at P = 0.01) and warranted tactical revaccination for its control. The study highlighted the fact that strain R1215 which had been isolated from the oesophageal-pharyngeal swabs of asymptomatic carrier cattle had a narrow serological spectrum suggesting that such viruses could be unsuitable as vaccine for the national campaign.     

Serological and biochemical analysis of foot-and-mouth disease virus (serotype C3) isolated in Argentina between 1981 and 1986

The evolution in the field is described for foot-and-mouth disease viruses belonging to serotype C₃ in Argentina between 1981 and 1986. During 1981 and 1982 only three isolations of this serotype took place, which showed minor serological and biochemical variations from the prototype strain C₃ Resende-Brasil/55. At the beginning of 1983 an outbreak was detected in a restricted geographical region caused by strains which had important serological and biochemical differences from the prototype strain. However, revaccination of the animals with the available commercial vaccine was sufficient to control the disease. During 1984 and up to 1986, a new outbreak of the same serotype took place in an extended geographical region of Argentina. During this outbreak, two field strains were isolated, studied and later included in the vaccine. One of them, strain C84, was a serological variant of the prototype strain and its inclusion in the vaccine had only a limited effect in controlling the disease. Inclusion of the other representative strain, C85, together with virus C84 finally reduced the number of outbreaks to the usual number reported.     

A serological evaluation of 1979-1982 Kenyan foot-and-mouth disease type SAT 2 viruses.

Serological evaluations of foot-and-mouth disease type SAT 2 viruses isolated in Kenya between 1979 and 1982 were performed using the two-dimensional microneutralization test. Nine field isolates of epizootiological significance were compared with four vaccine viruses. The results obtained identified Tan 5/68 as the most appropriate reference vaccine virus strain since it had the broadest serological spectrum. Potent Tan 5/68 vaccines would be expected to provide adequate protection against the contemporary SAT 2 field viruses. In the case of K183/74, which also was shown to have a broad spectrum with viruses isolated in Kenya, the results show that the 1982 isolate from central Kenya was significantly divergent (r less than 1.00 at P = 0.01) and warranted tactical revaccination for its control. The study highlighted the fact that strain R1215 which had been isolated from the oesophageal-pharyngeal swabs of asymptomatic carrier cattle had a narrow serological spectrum suggesting that such viruses could be unsuitable as vaccine for the national campaign.     

The interference effect of maternally-derived antibodies on the serological performance of pigs immunized with a foot-and-mouth disease oil emulsion vaccine

To control foot-and-mouth disease (FMD) outbreaks that originated in Jincheon County in South Korea between 2014 and 2015, several commercial vaccines were studied for their efficacy and serological performance in the field. In this study, the efficacy of the O SKR 7/10 vaccine was evaluated by challenge with the FMD virus (FMDV) O/Jincheon/SKR/2014 (O Jincheon), which has the same O/SEA/Mya-98 lineage as the O/SKR/7/10 strain that was isolated in 2010 in South Korea, in FMD-seronegative pigs. Full protection against the O Jincheon virus was demonstrated as early as 14 days postvaccination, which was explained by the strong serological relationship (r₁ value: ≥ 0.92) between the O Jincheon and O SKR 2010 viruses. However, in the field trial, no satisfactory serological elevations against FMDV were observed, even in the double-vaccinated groups. Therefore, it can be concluded that the O SKR 7/10 vaccine may need to be improved to overcome the interference effects from the high levels of maternally-derived antibodies generated due to the mandatory nationwide vaccination of sows in South Korea.     

Vaccination challenge studies with variants of street rabies virus isolated in Nigeria

In a preliminary study it was observed that adult ICR mice immunized with serial dilutions of an inactivated experimental human rabies vaccine from the Pitman-Moore (PM) vaccine virus were well protected against challenge with homologous virulent PM virus and challenge virus standard (CVS). However only one of five variant representatives in five of seven groups of 41 isolates of street rabies virus from Nigeria characterized by hybridoma monoclonal antibodies specific for the nucleocapsid and glycoprotein antigens of rabies virion was protected for by the vaccine. Guinea pigs immunized with a live attenuated low egg passage (LEP, Flury strain) vaccine currently used in canine vaccination in Nigeria protected against challenge with all five variants. The LEP vaccine protected against the variants and CVS quite well even when 1:125 dilution of the vaccine was used.     

Genetic and antigenic relationship of foot–and–mouth disease virus serotype O isolates with the vaccine strain O1/BFS

Foot–and–mouth disease serotype O viruses (FMDV/O) are responsible for the most outbreaks in FMD endemic countries. O1/BFS is one of the recommended FMD/O vaccine strains by World Reference Laboratory for FMD. In the current study, FMDV/O1 BFS vaccine strain and serotype O field isolates (45) were analyzed phylogenetically and antigenically to gain more insight into the genetic and antigenic characteristics of the vaccine strain and field isolates.O1/BFS showed similarity with 89% of the field isolates using a virus neutralization test (VNT). The P1 region encoding the FMDV capsid was sequenced and analysed for 46 strains of FMDV/O. Phylogenetic analysis showed these viruses originated from five continents and covered eight of 11 reported topotypes. Five isolates that demonstrated low antigenic similarities with O1/BFS were analyzed for their antigenic variation at the known neutralizing antigenic sites. Three of the five isolates demonstrated unique amino acid substitutions at various antigenic sites. No unique amino acid substitutions were observed for the other two unmatched isolates. Positively selected residues were identified on the surface of the FMD virus capsid supporting that it is important to continuously monitor field isolates for their antigenic and phenotypic changes.In conclusion, the vaccine strain O1/BFS is likely to confer protection against 89% of the 45 FMDV/O isolates based on VNT. Thus O1/BFS vaccine strain is still suitable for use in global FMD serotype O outbreak control. Combining data from phylogenetic, molecular and antigenic analysis can provide improvements in the process of vaccine selection.     

Clinical and virological evaluation of the efficacy of an inactivated EHV1 and EHV4 whole virus vaccine (Duvaxyn EHV1,4). Vaccination/challenge experiments in foals and pregnant mares.

Pregnant mares and young foals were vaccinated with Duvaxyn EHV1,4, an inactivated and adjuvanted vaccine containing both the EHV-1 and 4 antigens. SN and CF antibody titres were induced two weeks after first vaccination. Antibody levels were boosted after second vaccination, however they never reached the levels induced after virus challenge. Young foals were challenged with virulent EHV-1 and EHV-4 field viruses. Pregnant mares were challenged with the highly abortigenic EHV-1 strain Ab4. Vaccinated animals showed a clear reduction in clinical signs and virus excretion compared to unvaccinated control animals. Log transformed antibody levels could be correlated to duration of virus excretion. The incidence of EHV-1 induced abortions was drastically reduced in vaccinated mares. Therefore, although vaccinated animals are not fully protected against disease, Duvaxyn EHV1,4 clearly reduces clinical symptoms, the duration of virus shedding and the quantity of virus shed. It can be concluded that vaccination of foals and pregnant mares with Duvaxyn EHV1,4 significantly reduces the risk of abortions and outbreaks of respiratory disease caused by circulating field viruses.     

Efficacy of a high-potency multivalent foot-and-mouth disease virus vaccine in cattle against heterologous challenge with a field virus from the emerging A/ASIA/G-VII lineage

In 2015, outbreaks of foot-and-mouth disease (FMD) in the Middle East were discovered to be caused by a viral lineage (A/ASIA/G-VII), which has recently emerged from the Indian sub-continent. In vitro vaccine matching data generated by the World Reference Laboratory (WRLFMD) indicated that A/ASIA/G-VII field viruses were poorly matched with vaccines (A-SAU-95, A22 IRQ and A-IRN-05) that are already used in the region. In order to assess the likely performance of one of these commercially available FMD vaccines, sixteen cattle were vaccinated with a polyvalent vaccine which contained two serotype A components (A-SAU-95 and A-IRN-05) with a homologous potency of at least 6PD₅₀, and two cattle were left unvaccinated as controls. Twenty-one days later, all 18 cattle were challenged by tongue inoculation with an FMDV field isolate A/IRN/22/2015 from the A/ASIA/G-VII lineage, in line with the European Pharmacopeia PPG test conditions. The two control animals developed generalised FMD, and 7/16 vaccinated animals developed at least one foot lesion, thus only 56.3% were defined as protected. For the vaccine components, there was a significant increase in the probability of protection with increasing serological titres for A-SAU-95 (p = 0.03), but not for A-IRN-05 (p = 0.42). Analysis of FMDV in blood and nasal swabs suggested that vaccination reduced shedding and potential onward spread of FMD virus even if the animal developed foot lesions. In summary, the results from this study suggest that whilst this vaccine would not be appropriate for use in an emergency situation (in previously FMD-free countries), it may be partially effective in the field in endemic countries where repeat prophylactic vaccination is practiced. For emergency reactive vaccination, the findings from this study support the idea that a new vaccine strain should be developed that is tailored to the A/ASIA/G-VII lineage.     

Differentiation of the mumps vaccine strains from the wild viruses by the nucleotide sequences of the P gene

Nucleotide sequence analysis of a part of the P gene of mumps virus allowed the differentiation of live attenuated mumps vaccine strains from each other and from wild mumps viruses. Restriction enzyme analysis was found to serve as a convenient method of screening for one strain of mumps vaccine. Examination by the method of virus isolates obtained from the patients who developed mumps parotitis or meningitis following vaccination revealed that most of those viruses were related to the respective vaccine viruses used for immunization.     

Recombinant virus-expressed bovine cytokines do not improve efficacy of a bovine herpesvirus 1 marker vaccine strain

Cytokines play a key role as regulators of the immune response. To elucidate whether the efficacy of a live virus vaccine can be improved by co-expression of cytokines, expression cassettes for bovine interleukins (boIL)-2, -4, -6, and -12 and bovine interferon-gamma (boIFN-gamma) were integrated into the glycoprotein E (gE)-locus of the bovine herpesvirus 1 (BHV-1) vaccine virus strain GK/D. Cell culture analyses demonstrated that expression of the cytokines did not impair the replication of the recombinant viruses. To test safety and efficacy, groups of 4-6 months old BHV-1 seronegative calves were vaccinated intranasally with the parental virus strain GK/D or the recombinants, and challenged intranasally 3 weeks later with virulent BHV-1. The animals were monitored for clinical signs, virus excretion and antibody status after vaccination and challenge. All vaccines were well tolerated and protected the immunised calves from clinical disease following challenge, and reduced duration and titres of challenge virus shedding. Calves inoculated with the boIL-6, boIL-12 and boIFN-gamma expressing recombinants showed a significant reduction in vaccine virus shedding but secreted more challenge virus than the other vaccinees. These findings indicate that expression of these cytokines mediates a better control of the vaccine virus replication which, however, interferes with the immunogenicity of the vaccine. In summary, all recombinant viruses were safe and effective, but protection afforded by the recombinants was not improved as compared to vaccination with the parental virus strain GK/D.     

Early protection against homologous challenge after a single dose of replication-defective human adenovirus type 5 expressing capsid proteins of foot-and-mouth disease virus (FMDV) strain A24

Previously we demonstrated that two doses of a replication-defective human adenovirus serotype 5 (Ad5) carrying the capsid (P1) and 3C protease coding regions of a laboratory strain of FMDV (A12) completely protected five of six swine challenged with homologous virus. The objective of the current study was to evaluate the efficacy of one dose of an Ad5-vectored vaccine expressing the P1 coding region of an FMDV field strain. A replication-defective Ad5 containing the P1 coding region of FMDV A24 and the 3C coding region of A12 (Ad5A24) was constructed and evaluated for its ability to induce neutralizing antibodies and protect swine against homologous challenge after a single vaccination. Animals were challenged 7, 14 or 42 days after vaccination. Control groups included animals inoculated with commercial vaccine or phosphate-buffered saline. All vaccinated swine were completely protected against homologous challenge at 7, 14 or 42 days after vaccination. Based on these results, we conclude that a single inoculation of Ad5-vectored vaccines could be used as a tool to control FMD in outbreak situations.     

Intranasally administered Endocine™ formulated 2009 pandemic influenza H1N1 vaccine induces broad specific antibody responses and confers protection in ferrets

Influenza is a contagious respiratory disease caused by an influenza virus. Due to continuous antigenic drift of seasonal influenza viruses, influenza vaccines need to be adjusted before every influenza season. This allows annual vaccination with multivalent seasonal influenza vaccines, recommended especially for high-risk groups. There is a need for a seasonal influenza vaccine that induces broader and longer lasting protection upon easy administration. Endocine™ is a lipid-based mucosal adjuvant composed of endogenous lipids found ubiquitously in the human body. Intranasal administration of influenza antigens mixed with this adjuvant has been shown to induce local and systemic immunity as well as protective efficacy against homologous influenza virus challenge in mice. Here we used ferrets, an established animal model for human influenza virus infections, to further investigate the potential of Endocine™ as an adjuvant. Intranasal administration of inactivated pandemic H1N1/California/2009 split antigen or whole virus antigen mixed with Endocine™ induced high levels of serum hemagglutination inhibition (HI) and virus neutralization (VN) antibody titers that were also cross reactive against distant swine viruses of the same subtype. HI and VN antibody titers were already demonstrated after a single nasal immunization. Upon intratracheal challenge with a homologous challenge virus (influenza virus H1N1/The Netherlands/602/2009) immunized ferrets were fully protected from virus replication in the lungs and largely protected against body weight loss, virus replication in the upper respiratory tract and pathological changes in the respiratory tract. Endocine™ formulated vaccines containing split antigen induced higher HI and VN antibody responses and better protection from body weight loss and virus shedding in the upper respiratory tract than the Endocine™ formulated vaccine containing whole virus antigen.     

Bovine herpesvirus-1: Evaluation of genetic diversity of subtypes derived from field strains of varied clinical syndromes and their relationship to vaccine strains

Bovine herpesvirus-1 (BoHV-1) causes significant disease in cattle. Control programs in North America incorporate vaccination with modified live viral (MLV) or killed (KV) vaccine. BoHV-1 strains are isolated from diseased animals or fetuses after vaccination. There are markers for differentiating MLV from field strains using whole-genome sequencing and analysis identifying single nucleotide polymorphisms (SNPs). Using multiple primer sets and sequencing of products permits association of BoHV-1 isolates with vaccines. To determine association between vaccine virus and strains isolated from clinical cases following vaccination, we analyzed 12 BoHV-1 isolates from animals with various clinical syndromes; 9 corresponded to BoHV-1.1 respiratory group. The remaining three corresponded to BoHV-1.2b, typically found in genital tracts of cattle. Four BoHV-1 isolates were identical to a vaccine strain; three were from post-vaccination abortion episodes with typical herpetic lesions whose dams had received MLV vaccine during pregnancy, and one from a heifer given a related MLV vaccine; Sequences of two respiratory isolates perfectly matched mutations characterizing RLB106 strain, a temperature sensitive mutant used in intranasal and parenteral vaccines. The last three respiratory strains clearly appeared related to a group of MLV vaccines. Previously the MLV vaccines were grouped into four groups based on SNPs patterns. In contrast with above-mentioned isolates that closely matched SNP patterns of their respective MLV vaccine virus, these 3 strains both lacked some and possessed a number of additional mutations compared to a group of MLV vaccine viral genome. Finding BoHV-1.2b in respiratory cases indicates focus should be given BoHV-1.2b as an emerging virus or a virus not recognized nor fully characterized in BRD.     

Antigenic and genetic comparison of foot-and-mouth disease virus serotype O Indian vaccine strain,O/IND/R2/75 against currently circulating viruses

Foot-and-mouth disease (FMD) virus serotype O is the most common cause of FMD outbreaks in India and three of the six lineages that have been described are most frequently detected, namely Ind2001, PanAsia and PanAsia 2. We report the full capsid sequence of 21 serotype O viruses isolated from India between 2002 and 2012. All these viruses belong to the Middle East–South Asia (ME–SA) topotype. The serological cross-reactivity of a bovine post-vaccination serum pool raised against the current Indian vaccine strain, O/IND/R2/75,was tested by virus neutralisation test with the 23 Indian field isolates, revealing a good match between the vaccine and the field isolates. The cross reactivity of the O/IND/R2/75 vaccine with 19 field isolates from other countries (mainly from Asia and Africa) revealed a good match to 79% of the viruses indicating that the vaccine strain is broadly cross-reactive and could be used to control FMD in other countries. Comparison of the capsid sequences of the serologically non-matching isolates with the vaccine strain sequence identified substitutions in neutralising antigenic sites 1 and 2, which could explain the observed serological differences.     

Antigenic characterization of influenza viruses produced using synthetic DNA and novel backbones

The global system for manufacturing seasonal influenza vaccines has been developed to respond to the natural evolution of influenza viruses, but the problem of antigenic mismatch continues to be a challenge in certain years. In some years, mismatches arise naturally due to the antigenic drift of circulating viruses after vaccine strain selection has already been made. In other years, antigenic differences between the vaccine virus and circulating viruses are introduced as part of the current system, which relies on the use of egg-adapted isolates as a starting material for candidate vaccine viruses (CVVs). Improving the current process for making vaccine viruses can provide great value. We have previously established a synthetic approach for rapidly generating influenza viruses in a vaccine-approved Madin Darby canine kidney (MDCK) cell line using novel, high-growth backbones that increase virus rescue efficiency and antigen yield. This technology also has the potential to produce viruses that maintain antigenic similarity to the intended reference viruses, depending on the hemagglutinin (HA) and neuraminidase (NA) sequences used for gene synthesis. To demonstrate this utility, we generated a panel of synthetic viruses using HA and NA sequences from recent isolates and showed by hemagglutination inhibition (HI) tests that all synthetic viruses were antigenically-like their conventional egg- or cell-propagated reference strains and there was no impact of the novel backbones on antigenicity. This synthetic approach can be used for the efficient production of CVVs that may be more representative of circulating viruses and may be used for both egg- and cell-based vaccine manufacturing platforms. When combined with mammalian cell culture technology for antigen production, synthetic viruses generated using HA and NA sequences from a non-egg-adapted prototype can help to reduce the potential impact of antigenic differences between vaccine virus and circulating viruses on vaccine effectiveness.