We report on three cases of symptomatic transmission of the L-Zagreb mumps vaccine virus from three vaccinated children to five adult contacts. The five contact cases were parents of the vaccinated children and presented with parotitis and in one case also with aseptic meningitis. The etiology of the contacts' illness was determined by viral culture, genomic sequencing, serology and epidemiological linking. Two of the vaccinated children developed vaccine associated parotitis as an adverse event three weeks following immunization. Symptoms in contact cases developed five to seven weeks after the vaccination of the children. The five contact cases, as well as the three children with adverse events recovered completely. The children had been vaccinated with MMR vaccine produced by the Institute of Immunology Zagreb, each of them with a different lot. One of the possible explanations for these adverse events is that the very low levels of wild mumps virus circulation in the last decade, combined with waning immunity in those who received one dose of vaccine or suffered from mumps in childhood, resulted in susceptible young adults and that this unique epidemiological situation allows us to detect horizontal transmission of mumps vaccine virus.
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... In very rare cases, the risk can be associated with the residual pathogenic potential of the vaccine virus which has been observed for some mumps vaccine strains and OPV. Symptomatic horizontal transmission of the vaccine virus has been recorded among previously healthy household members of the vaccinees after vaccination with L-Zagreb mumps vaccine strain (Atrasheuskaya et al. 2006(Atrasheuskaya et al. , 2012Kaic et al. 2008;Tesović et al. 2008). The use of the Sabin live attenuated OPV decreased the number of poliovirus infections by > 99%. ...
Inactivated and live attenuated vaccines have improved human life and significantly reduced morbidity and mortality of several human infectious diseases. However, these vaccines have faults, such as reactivity or suboptimal efficacy and expensive and time-consuming development and production. Additionally, despite the enormous efforts to develop vaccines against some infectious diseases, the traditional technologies have not been successful in achieving this. At the same time, the concerns about emerging and re-emerging diseases urge the need to develop technologies that can be rapidly applied to combat the new challenges. Within the last two decades, the research of vaccine technologies has taken several directions to achieve safe, efficient, and economic platforms or technologies for novel vaccines. This review will give a brief overview of the current state of the novel vaccine technologies, new vaccine candidates in clinical trial phases 1–3 (listed by European Medicines Agency (EMA) and Food and Drug Administration (FDA)), and vaccines based on the novel technologies which have already been commercially available (approved by EMA and FDA) with the special reference to pandemic COVID-19 vaccines.
• Vaccines of the new generation follow the minimalist strategy.
• Some infectious diseases remain a challenge for the vaccine development.
• The number of new vaccine candidates in the late phase clinical trials remains low.
... Despite a better antibody response to L-Zagreb, the vaccination with this strain had some side effects and complications. There were cases of post-vaccination encephalitis caused by the L-Zagreb strain, and some cases of horizontal transmission of the vaccine virus were reported (3,4). The Rubini strain was officially not recommended by scientific authorities due to a weakened antibody response in comparison with the other vaccine strains, and its effectiveness of 33% was deemed to be inadequate (5). ...
The incidence of mumps has decreased in many countries since the introduction of vaccination programmes, however, in the past decade a rapid increase in the disease occurrence has been reported worldwide. The reason for this situation is still not clear. We present the results of a serological survey carried out in the Eastern Bohemia Region of the Czech Republic during the years 2008-2012.
In total, 2,536 samples of 2,034 patients were examined during the study period. The study cohort was divided into two groups, one consisted of individuals born before the introduction of mandatory vaccination and the other one comprised individuals born after mandatory vaccination started. For the serology analyses the ELISA kits RIDASCREEN Mumpsvirus IgM and IgG (R-Biopharm®, Germany) were used.
Out of 2,536 samples (including paired sera), 23.9% (n=606) were positive and 12% (n=304) had equivocal results. Most of the positive samples were obtained from patients aged 17-20 years. Significantly more (p<0.05) positive patients were born after the start of the national vaccination programme (patient group 2) (22.8%) compared to those born before its start (patient group 1) (13.7%). Interestingly, the analysis of data showed that 75.3% of patients falling into group 1 had anti-mumps IgG antibodies, which means that they had contracted mumps, whilst 23.5% of patients of group 2 had undetectable IgG antibodies, even though they should have been vaccinated.
The data from our study, with a low number of positive samples in the first years of the study and an increase in the last two years, could suggest the occurrence of outbreaks every 4-6 years.
... Mumps is preventable by vaccination with live mumps viruses (MuV) that have been attenuated by passage in various cell substrates . MuV vaccine strains vary in protective efficacy, degree of attenuation  and adverse event profiles . A correlate of protection in terms of neutralising antibody has not been established  and an animal model which mimics human disease has yet to be identified . ...
Aim. A controlled study was carried out regarding horizontal transmission of the vaccine strain of parotitic virus (PV). Materials and methods. 20 couples took part in the study. Monitoring of both spouses was carried out for 42 days after a single vaccination of one of them, levels of specific IgM and IgG in sera and virus-neutralizing IgG in sera and saliva were studied in dynamics, PV RNA was also determined in sera and saliva samples. Amplified fragments of F, SH, NP and HN genes of PV were sequenced. Results. Transfer of PV vaccine strain was registered in all the couples except for one. Except a single contact spouse, all the rest demonstrated formation of a specific immune response. At month 4 of the observation, group of vaccinated spouses differed significantly from a group of contact spouses only by total content of specific IgG and their avidity. Conclusion. Horizontal transmission of PV strain was demonstrated in couples after vaccination of one of the spouses and resulted in formation of specific immunity in 95% of contact individuals.
Measles is one of the most contagious human diseases. Administration of the live attenuated measles vaccine has substantially reduced childhood mortality and morbidity since its licensure in 1963. The live but attenuated form of the vaccine describes a virus poorly adapted to replicating in human tissue, but with a replication yield sufficient to elicit an immune response for long-term protection. Given the high transmissibility of the wild-type virus and that transmission of other live vaccine viruses has been documented, we conducted a systematic review to establish if there is any evidence of human-to-human transmission of the live attenuated measles vaccine virus. We reviewed 773 articles for genotypic confirmation of a vaccine virus transmitted from a recently vaccinated individual to a susceptible close contact. No evidence of human-to-human transmission of the measles vaccine virus has been reported amongst the thousands of clinical samples genotyped during outbreaks or endemic transmission and individual case studies worldwide.
In this work we report the mumps vaccine virus shedding based on the laboratory confirmed cases of the mumps virus (MuV) infection. The likely epidemiological sources of the transmitted mumps virus were children who were recently vaccinated with the mumps vaccine containing Leningrad-Zagreb or Leningrad-3 MuV. The etiology of the described cases of the horizontal transmission of both mumps vaccine viruses was confirmed by PCR with the sequential restriction analysis.
Though mumps virus (MuV) is a monotypic virus, genetic variation between strains has been described. Viruses have been placed into genotypes designated A-L based on the nucleotide sequence of the small hydrophobic (SH) gene, which is the most variable gene in the mumps genome. Molecular characterisation of MuV is an important component of mumps surveillance because it can help identify the transmission pathways of the virus as well as distinguish between wild-type and vaccine strains. Here, we propose a standardized nomenclature and an analysis protocol for the genetic characterisation of mumps strains to facilitate expansion of molecular epidemiological studies. In addition to assigning standard reference strains for the recognized genotypes of MuV, a convention is proposed for naming for strains and criteria to designate a new genotype.
Two mumps virus strains 9218/Zg98 and Du/CRO05 were isolated in two locations in Croatia in 1998 and 2005, respectively. Genetic characterization of these temporally distinct mumps virus isolates was carried out in order to determine their genotype and putative antigenic relatedness to mumps virus vaccine strains. Sequence analysis of the small hydrophobic (SH) gene revealed that isolate 9218/Zg98 shows less than 95% of similarity to any reference strain, thus representing a potential reference strain for a new genotype. Isolate Du/CRO05 clearly belongs to genotype G with the 97% of homology to the reference strain Glouc1/UK96. When compared to each other, the two Croatian strains have extremely low level of homology of only 89% indicating no relatedness between them. Putative antigenic properties of the HN protein of these two isolates were compared to different vaccine strains. The results reveal a higher level of homology of antigenic determinants to non-A genotype vaccine strains than to A genotype vaccine strain.
In the frame of measles elimination activities, sera from 1205 Croatian citizens from all parts of the country and of all ages were tested, using Gull Laboratories ELISA, for measles IgG. Equivocal results were found in 50 subjects. Of the remaining 1155 participants, 118 or 10.2% were negative and 1037 or 89.8% positive. The proportion of seronegatives ranged from zero (age groups 41-50, 51 and more) up to 21.4% (1 year of age). As for their distribution into age groups suggested by the European Regional Office of WHO, there were 12.7, 8.9, 9.5 and 8.8% negatives in age groups 1-4, 5-9, 10-14 and 15 + years, respectively. According to these results, only the first two age groups meet WHO criteria, indicating that vaccination coverage higher than the reported 90-94% should be attained if one is to expect measles elimination.
Here we describe symptomatic transmission of the Leningrad-3 mumps vaccine virus from healthy vaccinees to previously vaccinated contacts. Throat swab and serum samples were taken from six symptomatic mumps cases and from 13 family contacts. Assessment of serum IgG and IgM anti-mumps virus antibodies and IgG avidity testing was performed using commercial test kits. Sera neutralizing antibodies were measured by plaque reduction neutralization assay using the L-3 vaccine mumps virus as the target. All six of the symptomatic mumps cases and three contact subjects tested positive for mumps by RT-PCR. The genomic sequences tested (F, SH and HN genes) of all nine of these samples were identical to the L-3 mumps vaccine strain. All 13 contacts were asymptomatic; however clear serological evidence of mumps infection was found in some of them. The likely epidemiological source of the transmitted L-3 mumps virus was children who were recently vaccinated at the schools attended by the six symptomatic mumps patients described here. The L-3 mumps vaccine virus can be shed and transmitted horizontally, even to subjects previously vaccinated with the same virus.
Mumps is not a mandatorily notifiable disease in Austria. However, in the first week of May 2006, a sudden increase in serologically confirmed cases of mumps, confined to three public health districts of the southern Austrian province of Carinthia, was identified by the Austrian Reference laboratory for MMR. An epidemiological investigation of this cluster of mumps cases was performed. A total of 214 cases fulfilled the outbreak case definition; 143 cases were laboratory confirmed and 71 cases were epidemiologically linked and fulfilled the clinical picture of the case definition. The vaccination status was known for 169 patients. Nearly half of the cases for whom the vaccination status was known occurred in non-vaccinated persons, another 40% were vaccinated with one dose of the vaccine and 11% had received two doses. Only four mumps cases occurred in children aged 14 years or younger, indicating that the vaccination coverage and the acceptance of the recommended childhood vaccinations have strongly improved within the past 15 years. Vaccination scheme failure but not vaccine failure is primarily to blame for this mumps outbreak.
Adverse Events Following vaccination in Croatia in 2005 [in Croatian Available from
Kaic B. Ed. Adverse Events Following vaccination in Croatia in 2005 [in Croatian]. Zagreb: Croatian Institute of Public Health, 2006; 5. Available from: http://www.hzjz.hr/epidemiologija/nuspojave2005.pdf
Mumps outbreak in young adults following a festival in Austria Available from: http://www Citation style for this article Transmission of the L-Zagreb mumps vaccine virus
Schmid D, Holzmann H, Alfery C, Wallenko H, Popow-Kraupp Th, Allerberger F. Mumps outbreak in young adults following a festival in Austria, 2006. Euro Surveill 2008;13(7). Available from: http://www.eurosurveillance.org/edition/ v13n07/080214_6.asp This article was published on 17 April 2008. Citation style for this article: Kaic B, Gjenero-Margan I, Aleraj B, Ljubin-Sternak S, Vilibic-Cavlek T, Kilvain S, Pavic I, Stojanovic D, Ilic A. Transmission of the L-Zagreb mumps vaccine virus, Croatia, 2005-2008. Euro Surveill. 2008;13(16):pii=18843. Available online: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=18843
Adverse Events Following vaccination in Croatia in
Kaic B. Ed. Adverse Events Following vaccination in Croatia in 2005 [in
Croatian]. Zagreb: Croatian Institute of Public Health, 2006; 5. Available