Vaccine-derived Virus Research Articles

Effect of Natural Exposure to Vaccine-derived North American Genotype PRRS Virus on the Serological Response in Naïve Pigs

Diagnosis of porcine reproductive and respiratory syndrome virus (PRRSV) is often performed by serological testing, but ELISA does not differentiate between infections with wild-type or vaccine virus. Two attenuated live vaccines [European (EU) or North American (NA) genotype] are used. In addition to wild-type isolates, vaccine or vaccine-derived viruses occur frequently. This is often not considered when the ELISA results are used to differentiate between epizootic and enzootic infections. In this study, an infection with the NA genotype vaccine-derived virus was detected in two herds previously PRRSV negative and ELISA results [sample to positive (s/p) ratios] were analysed. The virus was identified by RT-PCR and nucleotide sequences of ORF5 had 97% (herd A) and 99% (herd B) identity with the genome of a ML PRRSV vaccine belonging to the NA genotype. Pigs of different age became positive with an average s/p ratio of 2.24 (A) and 1.18 (B). The data clearly demonstrate that spontaneous infection with a vaccine-derived virus of the NA genotype induces ELISA s/p ratios similar to those induced by vaccination or by infection with wild-type virus. We conclude that for a correct interpretation of serological results the circulation of vaccine or vaccine-derived virus isolates has to be excluded by RT-PCR, even if vaccination is not ongoing.

Genetic differentiation of the nucleocapsid protein of Korean isolates of porcine epidemic diarrhoea virus by RT-PCR based restriction fragment length polymorphism analysis

A reverse transcriptase polymerase chain reaction (RT-PCR) based restriction fragment length polymorphism (RFLP) analysis based on the nucleocapsid ( N) gene was developed to differentiate between field isolates of porcine epidemic diarrhoea virus (PEDV) and a vaccine strain, J-vac. Thirteen field isolates of PEDV from Korea were distinguishable from the vaccine strain and the prototype PEDV strain CV777 by RFLP using Tru9I. RFLP patterns in 11 of 13 field PEDV isolates were different from the vaccine strain using AspLEI, HgaI and MspR9I. Sequence analysis of the PEDV N gene revealed that Korean field PEDV isolates had 93.6% and 89.6% identity with the vaccine virus at nucleotide and amino acid sequence levels, respectively, suggesting progressive point mutations of the PEDV genome in the field. RFLP analysis of the PEDV N gene is a promising tool for distinguishing field strains from the vaccine-derived virus.

Detection of unusual mutation within the VP1 region of different re-isolates of poliovirus Sabin vaccine

In the present study, a genomic analysis of full VP1 sequence region of 15 clinical re-isolates (14 healthy vaccinees and one bone marrow tumor patient) was conducted, aiming to the identification of mutations and to the assessment of their impact on virus fitness, providing also insights relevant with the natural evolution of Sabin strains. Clinical re-isolates were analyzed by RT-PCR, sequencing and computational analysis. Some re-isolates were characterized by an unusual mutational pattern in which non-synonymous mutations outnumbered the synonymous ones. Furthermore, the majority of amino-acid substitutions were located in the capsid exterior, specifically in N-Ags, near N-Ags and in the north rim of the canyon. Also mutations, which are well-known determinants of attenuation, were identified. The results of this study propose that some re-isolates are characterized by an evolutionary pattern in which non-synonymous mutations with a direct phenotypic impact on viral fitness are fixed in viral genomes, in spite of synonymous ones with no phenotypic impact on viral fitness. Results of the present retrospective characterization of Sabin clinical re-isolates, based on the full VP1 sequence, suggest that vaccine-derived viruses may make their way through narrow breaches and may evolve into transmissible pathogens even in adequately immunized populations. For this reason increased poliovirus laboratory surveillance should be permanent and full VP1 sequence analysis should be conducted even in isolates originating from healthy vaccinees.

Characterization of field isolates of infectious laryngotracheitis virus from Ontario

Five cases of infectious laryngotracheitis (ILT) occurred in the fall of 2004 in the Niagara Peninsula, in Southern Ontario. At about the same time two more cases occurred in Eastern Ontario and one case in South-Western Ontario. We examined, at a molecular level, 10 Ontario ILT virus field isolates from 2004 and early 2005 as well as four ILT vaccine viruses by polymerase chain reaction-restriction fragment length polymorphism analyses of ICP4 and glycoprotein E genes, and partial sequencing of UL47 and glycoprotein G genes. We determined that the five Niagara Peninsula ILT viruses were identical among themselves. They represented an independent cluster of ILT cases and were not related to other cases that occurred during 2004 and early 2005. Viruses isolated during the outbreaks in Eastern and South-Western Ontario could not be differentiated from chicken embryo origin ILT vaccine viruses. Niagara Peninsula isolates were different, at a molecular level, from all four vaccine viruses that were examined and from ILT viruses that had been previously analysed and reported in the literature. Taken together our data indicate that both "wild-type" and vaccine-derived viruses are involved in ILT cases in Ontario.

The perspective of global eradication of poliomyelitis

In recent years, Germany and Switzerland have changed national policies to recommend vaccination with IPV (inactivated polio vaccine) instead of OPV (oral polio vaccine) for protection against poliomyelitis. An all IPV-schedule in routine childhood polio vaccination eliminates the - albeit minimal - risk of OPV-associated paralytic poliomyelitis. However, the impact of such a vaccination scheme on the goal to eventually eradicate poliomyelitis on a global level remains debatable. Published studies indicate that vaccine-derived poliovirus may persist in the environment for prolonged periods of time even after completion of a global eradication programme that relies on the near-exclusive use of OPV in the developing countries. Travellers vaccinated with IPV only might become silently infected with vaccine-derived virus, shedding it in large quantities. We therefore plead for a vaccination schedule that includes at least one last dose of OPV to induce strong mucosal immunity.

Pertussis is back and now what?

AbstractVaccination is one of the most successful tools for controlling infectious diseases. Today millions of lives are saved because of vaccination against tetanus, diphtheria, whooping cough, poliomyelitis, meningitis, measles. Although it is generally perceived as the “golden solution,” it has been shown recently that the extensive use of vaccines may lead to undesirable effects (e.g., poliomyelitis epidemics due to vaccine-derived viruses) or the resurgence of a disease (e.g., reemergence of whooping cough after 40 years of vaccination). In the documented cases, epidemiological studies clearly indicate that extensive vaccination can induce modifications of pathogens over time, the emergence of new pathogens due to changes in ecosystems, or change in the transmission of the disease. Therefore, to optimize the benefits of immunization programs and prevent global adverse effects of vaccines (and the subsequent detrimental impact to the general public), the consequences of extensive vaccinations on the pathogen, ecosystem, and/or human host populations remain to be evaluated.KeywordsVaccine StrainPertussis ToxinPertussis VaccineBordetella PertussisWhooping CoughThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Poliovirus detection in wastewater and stools following an immunization campaign in Havana, Cuba.

Recent outbreaks of poliomyelitis caused by vaccine-derived virus have raised concerns that vaccine-derived poliovirus may continue to circulate after eradication. In these outbreaks, the virus appears to have replicated for > or =2 years before detection. Early detection is critical for an effective response to these outbreaks. Although acute flaccid paralysis (AFP) surveillance will remain the standard for poliovirus detection, wastewater sampling could be a useful supplement. In this study, we evaluated the sensitivity of wastewater sampling by concurrently collecting stools from children aged < 3 years attending two neighbourhood clinics in Havana, Cuba, and wastewater from the same neighbourhoods. Sample collection was begun during the third week after the national immunization campaign, continued weekly through the seventh week, and was repeated during weeks 15 and 19. Virus detection and titration were performed using both cell culture and polymerase chain reaction techniques. Wastewater sampling was found to be at least as sensitive as stool sampling under these conditions. Poliovirus was isolated from children through week 7, suggesting that viral shedding reached undetectable levels between weeks 8 and 14. The last virus-positive wastewater sample was collected during week 15. Wastewater sampling under the conditions studied can be a sensitive supplement to AFP surveillance. Similar studies under different conditions are needed to determine the role of wastewater sampling in post-eradication surveillance.

Experimental inoculation of late term pregnant sows with a field isolate of porcine reproductive and respiratory syndrome vaccine-derived virus

The use of a live attenuated porcine reproductive and respiratory syndrome virus (PRRSV) vaccine in piglets has been associated with reproductive disorders in non-vaccinated sows. Vaccine-derived virus (VDV) has been isolated from foetuses, stillborn pigs, and dead piglets, indicating that the live vaccine spread from vaccinated piglets to non-vaccinated sows, and that the virus might be implicated in the severe reproductive problems observed. In the present study, one such VDV isolate was used to experimentally infect pregnant sows in the last trimester. The chosen isolate, which had more than 99.6% identity to the attenuated vaccine virus, originated from the lungs of a stillborn pig from a swine herd with a sudden high level of stillborn pigs and increased piglet mortality in the nursing period. Intranasal inoculation of sows with the virus isolate resulted in congenital infection, foetal death, and preweaning pig mortality. As such, the present study showed that vaccine-derived PRRSV can cause disease in swine consistent with PRRS.

Persistence of vaccine-derived poliovirus following a mass vaccination campaign in Cuba: implications for stopping polio vaccination after global eradication.

With substantial progress made toward polio eradication, developing the appropriate strategy for discontinuing global oral poliovirus vaccine (OPV) after global eradication becomes increasingly important. At issue is the theoretical risk of independent circulation of potentially virulent OPV-derived strains. Because Cuba uses OPV only in mass campaigns, it represents an ideal site to assess vaccine-derived poliovirus persistence. Infants born after the 1997 biannual mass campaigns were evaluated for past (neutralizing antibody) or current (virus excretion) evidence of vaccine-derived poliovirus exposure. We obtained sera and/or stool specimens from 861 infants; a second serum from 218 infants. All stool specimens were poliovirus negative. Of 762 infants, 113 (14.8%) had initially detectable poliovirus type 1 antibody, 193 (25.3%) type 2, and 94 (12.3%) type 3. A precipitous antibody decline occurred in initially positive sera. Our results suggest that in a country with high population immunity, vaccine-derived virus is unlikely to establish ongoing circulation.

Herpes zoster in three healthy children immunized with varicella vaccine (Oka/Biken); the causative virus differed from vaccine strain on PCR analysis of the IV variable region (R5) and of a PstI-site region.

This study was undertaken to determine whether the causative virus was a vaccine-derived or wild-type virus when zoster occurred in healthy children immunized with varicella vaccine (Oka/Biken). The DNAs of clinical isolated strains and vaccine strain (Oka/Biken) were analyzed by the polymerase chain reaction with two sets of primers for the variable region IV (R5 tandem direct reiterations, TDR) and for the region with a PstI site in a middle portion of the long unique segment of the varicella zoster virus genome. Of six zoster patients after vaccination with Biken, three clinical isolates were examined and had two copies in R5 TDR and were PstI-site positive. Therefore, these strains were different from the vaccine-type strain (Oka/Biken), which had two copies in R5 TDR and was PstI-site-negative. The mean age of onset of zoster was 4 years. The mean age of vaccination was 25 months. The mean interval between vaccination and onset of zoster was 22 months. Hence the results indicate that the causative virus of zoster in healthy children immunized with varicella vaccine (Oka/Biken) was wild type and differed from the vaccine strain. Some vaccinees probably do not have protective immunity for a long time after immunization because the mean interval between vaccination and onset of zoster was 22 months.

Search for optimal parent for recombinant vaccinia virus vaccines. Study of three vaccinia virus vaccinal strains and several virus lines derived from them

Three vaccinia virus strains (Praha, DD—a DRYVAX Wyeth vaccine-derived virus—and LIVP) were examined for growth in various cell cultures and for virulence and immunogenicity in mice. The viruses did not differ by their growth rats in monkey kidney cells (CV-1), human diploid cells (LEP), rat TK − cells (RAT2) or primary dog kidney cells. The immunogenicity of Praha and DD viruses was similar, the virus LIVP was somewhat more immunogenic. In terms of virulence in 3-day-old mice, the DD virus was the most attenuated. Single-plaque progenies were derived from the original smallpox vaccines VARIE Sevac (strain Praha) and DRYVAX Wyeth and tested for the above markers and DNA restriction patterns. The results obtained demonstrated biological and molecular heterogeneity of the original virus populations. Close linkage was observed between immunogenic activity and virulence in 3-day but not in 3-week mice. The results indicate that smallpox vaccine preparations may serve as an abundant source of virus mutants.

Differentiation between wild and vaccine-derived strains of poliovirus by stringent microplate hybridization of PCR products

Procedures for differentiation between wild and vaccine-derived strains of poliovirus are required, particularly in countries where wild and vaccine-related strains coexist. For this differentiation, we tested the method of Inouye and Hondo (S. Inouye and R. Hondo, Arch. Virol. 129:311-316, 1993) for discrimination of closely related viruses by using stringent microplate hybridization of PCR products. We used a pair of primers with enterovirus common sequences (between these primers there is a variable region for capsid proteins) for PCR using templates from wild and vaccine-derived poliovirus strains which were isolated in tissue culture and serotyped by neutralization assay. We also used the same primers for preparation of probes, which were labelled by incorporation of biotin-dUTP in the PCR, with the three original Sabin vaccine virus strains used as templates. The amplified DNAs from the isolates were immobilized on microplate wells and were then hybridized with the labelled probes. We found that, under the usual hybridization conditions, the Sabin vaccine virus strain probes hybridized with both wild and vaccine-derived viruses, but under stringent conditions, they reacted only with vaccine-derived viruses of the same serotype, clearly differentiating these from wild-type viruses.

Genetic stability of Sabin strain of type 3 poliovirus in the sensitivity to inhibitory bovine serum. I. Selection of inhibitory bovine serum against type 3 Sabin strain and sensitivity to the serum of vaccine progenies.

Investigations were carried out on the identification and genetic stability of type 3 Sabin vaccine (Leon 12 a1b) strain using a bovine inhibitor marker.Sera with strong inhibitory activity to the virus were rarely found in calves, while with high frequencies in heifers, and found to be reduced slightly in number at advanced ages.Of 495 sera tested, two (BS-19 and BE-19) specifically neutralized 3 laboratory strains of type 3 poliovirus including Leon 12 a1b, and left wild virus strains of the same type entirely unaffected. The strain-specific reactivity of the inhibitory sera was clearly demonstrated in the kinetic neutralization test.In vitro or human passage progenies of the vaccine virus were investigated for their sensitivity to the two bovine sera. While both the vaccine virus and its progenies were equally sensitive to BS-19, the progenies were less sensitive than the original vaccine virus to the inhibition by BE-19.On the basis of these results, the practical utility of bovine inhibitor marker for the identification of vaccine-derived viruses was discussed.