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Vaccination is the only guarantee for elimination of measles infection. Healthcare workers have a 13- to 19-fold higher risk for contracting measles than the general population. The number of individuals in the population who did not respond to vaccination is up to 10%, and their accumulation may lead to an outbreak of the infection. The aim of our research was to find potential predictors of arising post-vaccination measles antibodies in the panel of biochemical and immunological serum markers in healthcare workers. The group of healthcare workers (n = 76) aged from 19 to 51 years, with proven absence of pre-existing anti-measles antibodies were twice vaccinated 3 months apart with live measles culture vaccine (SPA “Microgen”, Russia). Measles-specific IgG, total IgG, IgM, IgA, IFNγ, IL-6, CRP, total protein, ALT, AST, total bilirubin, urea, creatinine, protein fractions were determined before vaccination, 1 month after vaccination, 1 month following revaccination, 1 year after revaccination. ROC analysis was used to gain access to the diagnostic performance of quantitative variables in predicting a categorical outcome. Development of a predictive probability model for the binary outcome was carried out using logistic regression. IFNγ, total IgG, IgM, total bilirubin, ALT activity at various post-immunization stages may be considered potential laboratory predictors of measles vaccination failures in healthcare workers. Meanwhile, the contents of pre-vaccination IFNγ, and IgG to measles virus after first vaccination proved to be most informative indexes, which formed the basis for the development of regression models predicting the risk of both primary and secondary vaccination failures. These models allowed to develop algorithm for predicting failures of the measles vaccination in healthcare workers that can be used for detection of persons at risk for non-forming specific humoral immunity. This algorithm is primarily focused on search for the persons who have not responded to measles vaccination, including subjects with probable immunodeficiency conditions. We do not exclude that, on the basis of revealed predictors following measles vaccination, it would be possible to build prognostic models of vaccination efficiency for other vaccinemanaged infections.

Fowlpox (FP) is an enzootic viral disease that infects domestic and wild birds globally. Although commercial poultry flocks have been vaccinated since the beginning of the last century, reports of outbreaks of the disease in vaccinated flocks have been accumulating, mainly in recent years. There are several hypotheses regarding the causes of fowl pox vaccine failure, but no re-examination of the process of vaccination in today's commercial flocks has been reported. After several cases of vaccination failure in vaccinated flocks, the authors of the article identified a critical problem with the conventional wing web (WW) stab vaccination method. A primary feasibility study was followed by a series of controlled field studies comparing the safety and efficacy of the traditional vaccination method of WW stab to the subcutaneous injection. The subcutaneous application was tested using a one dose per bird in different volumes. The studies were carried out in commercial rearing farms for layers and heavy breeders in Israel. The controlled field studies under commercial conditions included more than 20,000 birds. The results demonstrated that vaccination of pox vaccine by subcutaneous injection is completely safe, much faster, and more reliable than the WW stab vaccination method, providing a better and uniform immune response and protection and should be considered as an optional method for Fowlpox vaccination in large commercial poultry flocks. [ABSTRACT FROM AUTHOR]

Abstract The H9N2 subtype avian influenza virus (AIV) inactivated vaccine has been used extensively in poultry farms, but it often fails to stimulate a sufficiently high immune response in poultry in the field, although it works well in laboratory experiments; hence, the virus still causes economic damage every year and poses a potential threat to public health. Based on surveillance data collected in the field, we found that broilers with high levels of maternal-derived antibodies (MDAs) against H9N2 virus did not produce high levels of antibodies after vaccination with a commercial H9N2 inactivated vaccine. In contrast, specific pathogen-free (SPF) chickens without MDAs responded efficiently to that vaccination. When MDAs were mimicked by administering passively transferred antibodies (PTAs) into SPF chickens in the laboratory, similar results were observed: H9N2-specific PTAs inhibited humoral immunity against the H9N2 inactivated vaccine, suggesting that H9N2-specific MDAs might hinder the generation of antibodies when H9N2 inactivated vaccine was used. After challenge with homologous H9N2 virus, the virus was detected in oropharyngeal swabs of the vaccinated and unvaccinated chickens with PTAs but not in the vaccinated chickens without PTAs, indicating that H9N2-specific MDAs were indeed one of the reasons for H9N2 inactivated vaccine failure in the field. When different titers of PTAs were used to mimic MDAs in SPF chickens, high (HI = 12 log2) and medium (HI = log 9 log2) titers of PTAs reduced the generation of H9N2-specific antibodies after the first vaccination, but a booster dose would induce a high and faster humoral immune response even of PTA interference. This study strongly suggested that high or medium titers of MDAs might explain H9N2 inactivated vaccine failure in the field.

• Over 2/3 vertically HIV individuals lack rubella antibodies 16y after vaccination. • There is a 7% higher chance of rubella seronegativity for each y of the last dose. • 80.6% rubella seronegative vertically HIV individuals respond to an extra MMR dose. Very limited data are available on the persistence of rubella antibodies in vertically HIV-infected individuals who were vaccinated early in life. Prospective, cohort study on 4 groups of patients: 96 vertically HIV-1-infected individuals (v-HIV), 69 horizontally HIV-1-infected individuals (h-HIV), 93 healthy controls previously vaccinated for rubella (vac-CON) and 20 healthy controls with history of rubella disease (dis-CON). A blood sample was collected and rubella antibodies were analyzed by ELISA. Rubella antibodies above 10 IU/mL were considered protective. Individuals with seronegative results were offered an extra MMR vaccine dose and were tested at least 30 days afterwards. Time since previous rubella vaccination was similar in v-HIV, h-HIV and vac-CON (16, 11 and 11 years; p = 0.428). v-HIV and h-HIV were also comparable regarding median CD4 T cells (613 and 614 cells/mm3; p = 0.599) and percentage on ART (93.8% and 98.6%; p = 0.135) at study entry. v-HIV had less individuals on virological suppression (63.5%) compared to 85.5% in h-HIV (p < 0.001). Rubella seropositivity and antibodies were significantly lower in v-HIV compared to h-HIV (32.3% vs 65.5%, 4.3 IU/mL vs 21.1 IU/mL; p < 0.001). Time interval between the last rubella vaccine dose and study entry was associated with an increase of rubella seronegativity, with a 7% higher chance of seronegativity for each one-year increase. After an extra MMR dose, 40 out of 48 (83.3%) seronegative individuals responded, with no significant difference among groups considering rubella seropositivity and antibody levels. As vertically HIV-infected individuals reach adolescence and adulthood, assessment of vaccine antibodies can identify those who might benefit from an extra vaccine dose. [ABSTRACT FROM AUTHOR]

The global spread of avian influenza virus (AIV) of clade 2.3.4.4b since 2016 has caused severe losses in wild birds and poultry and has posed a risk for the infection of mammals including humans. The vaccination of poultry has been used to limit the spread of the virus and mitigate its socioeconomic impact. Here, we describe H5N8 epidemics in chickens, turkeys and ducks from different localities in Egypt from 2019 to 2021. About 41.7% (n = 88/211) flocks were tested positive by RT-qPCR for H5N8 viruses with prevalence rates of 45.1% (n = 65/144) and 34.3% (n = 23/67) in vaccinated and non-vaccinated flocks, respectively. A sequence analysis of the hemagglutinin and neuraminidase genes indicated not only the multiple introduction events of H5N8 viruses in Egypt but also the establishment of endemic viruses in commercial poultry in 2020/2021. The recent H5N8 viruses in poultry in Egypt are genetically distinct from the majority of licensed vaccines used in the field. Together, our findings indicate that poultry in Egypt is an endemic center for clade 2.3.4.4b in the Middle East. The efficiency of current vaccines should be regularly evaluated and updated to fully protect poultry flocks in Egypt against H5N8 viruses. [ABSTRACT FROM AUTHOR]

The aim of this study is to determine the effect of repeated vaccinations on neutralizing SARS-CoV-2 IgG antibody titers, evaluate risk factors for immunological non-response, and to report breakthrough infections in chronic hemodialysis patients. Methods: A prospective, multi-center cohort study in 163 chronic hemodialysis patients was conducted. Antibody titers were measured three months after second, third, and fourth (10 pts) booster vaccinations. SARS-CoV-2 neutralizing antibody titers in BAU/mL and % inhibition were divided into three categories (<216, 216–433, >433 and <33, 33–66, and >66%). Somers's test, paired t-test, and univariable and multivariable logistic regression analysis were applied to evaluate differences in antibody levels and search for risk factors for vaccination failure defined as neutralizing titers <50% and/or need for repeated booster vaccinations. Furthermore, we report on a case series to describe characteristics of patients after four vaccinations (n = 10) and breakthrough infections (n = 20). Results: Third dose boosters resulted in higher proportions of patients with neutralizing antibody levels >66% as compared to after the second dose (64.7% after second dose vs. 88.9% after third dose, p = 0.003), as well as in a respective increase in neutralizing titer levels in % from 68 ± 33% to 89 ± 24 (p < 0.001). The proportion of patients with IgG-titers below 216 BAU/mL decreased from 38.6 to 10.5% (p ≤ 0.001). Age (p = 0.004, OR 1.066, 95% CI 1.020–1.114) and presence of immunosuppressive medications (p = 0.002, OR 8.267, 95% CI 2.206–30.975) were identified as major risk factors for vaccination failure. Repeated booster vaccinations ≥4 times were effective in 8 out of 10 former low-responders (80%) without any side effects or safety concerns. Breakthrough infections showed a clinically mild course but were associated with prolonged viral shedding on PCR-testing ranging 7–29 (mean 13) days. Conclusions: Third and fourth mRNA-based booster vaccinations resulted in higher and longer lasting SARS-CoV-2 antibody levels as compared to after two dosages. The presence of immunosuppressive medication and repeat vaccinations are major potentially modifiable measures to increase antibody levels in non-or low-responders. Breakthrough infections with SARS-CoV-2 Omicron were associated with prolonged viral shedding but clinically mild disease courses. [ABSTRACT FROM AUTHOR]

Despite the existence of an effective live-attenuated vaccine, measles can appear in vaccinated individuals. We investigated breakthrough measles cases identified during our surveillance activities within the measles/rubella surveillance network (MoRoNet) in Milan and surrounding areas (Northern Italy). Between 2017 and 2021, we confirmed measles virus (genotypes B3 or D8) infections in 653 patients and 51 of these (7.8%) were vaccinees. Among vaccinated individuals whose serum was available, a secondary failure was evidenced in 69.4% (25/36) of cases while 11 patients (30.6%) were non-responders. Non-responders were more frequently hospitalized and had significantly lower Ct values in both respiratory and urine samples. Median age and time since the last immunization were similar in the two groups. Importantly, we identified onward transmissions from vaccine failure cases. Vaccinees were involved in 20 outbreaks, in 10 of them they were able to transmit the virus, and in 8 of them, they were the index case. Comparing viral hemagglutinin sequences from vaccinated and non-vaccinated subjects did not show a specific mutation pattern. These results suggest that vaccination failure was likely due to the poor immune response of single individuals and highlights the importance of identifying breakthrough cases and characterizing their clinical and virologic profiles. [ABSTRACT FROM AUTHOR]

Measles is a highly infectious viral exanthema very rarely seen in children under 9 months, as well as adults. We describe a case of measles in a 29-day old infant who presented with fever, rash and pneumonia. Treatment commenced with IV antibiotics, IVIG and oral Vitamin A following admission to the ICU. The mother had a similar illness prior to the onset of symptoms in the baby. She had not received MCV as per schedule. The infant and mother recovered fully without any complications. We conclude that administering one dose of MCV to a woman who has not taken at least two doses of MCV- at least three months prior to conception may help in preventing measles in the infant in first nine months of life.

The global spread of avian influenza virus (AIV) of clade 2.3.4.4b since 2016 has caused severe losses in wild birds and poultry and has posed a risk for the infection of mammals including humans. The vaccination of poultry has been used to limit the spread of the virus and mitigate its socioeconomic impact. Here, we describe H5N8 epidemics in chickens, turkeys and ducks from different localities in Egypt from 2019 to 2021. About 41.7% (n = 88/211) flocks were tested positive by RT-qPCR for H5N8 viruses with prevalence rates of 45.1% (n = 65/144) and 34.3% (n = 23/67) in vaccinated and non-vaccinated flocks, respectively. A sequence analysis of the hemagglutinin and neuraminidase genes indicated not only the multiple introduction events of H5N8 viruses in Egypt but also the establishment of endemic viruses in commercial poultry in 2020/2021. The recent H5N8 viruses in poultry in Egypt are genetically distinct from the majority of licensed vaccines used in the field. Together, our findings indicate that poultry in Egypt is an endemic center for clade 2.3.4.4b in the Middle East. The efficiency of current vaccines should be regularly evaluated and updated to fully protect poultry flocks in Egypt against H5N8 viruses.

Despite the existence of an effective live-attenuated vaccine, measles can appear in vaccinated individuals. We investigated breakthrough measles cases identified during our surveillance activities within the measles/rubella surveillance network (MoRoNet) in Milan and surrounding areas (Northern Italy). Between 2017 and 2021, we confirmed measles virus (genotypes B3 or D8) infections in 653 patients and 51 of these (7.8%) were vaccinees. Among vaccinated individuals whose serum was available, a secondary failure was evidenced in 69.4% (25/36) of cases while 11 patients (30.6%) were non-responders. Non-responders were more frequently hospitalized and had significantly lower Ct values in both respiratory and urine samples. Median age and time since the last immunization were similar in the two groups. Importantly, we identified onward transmissions from vaccine failure cases. Vaccinees were involved in 20 outbreaks, in 10 of them they were able to transmit the virus, and in 8 of them, they were the index case. Comparing viral hemagglutinin sequences from vaccinated and non-vaccinated subjects did not show a specific mutation pattern. These results suggest that vaccination failure was likely due to the poor immune response of single individuals and highlights the importance of identifying breakthrough cases and characterizing their clinical and virologic profiles.

Background Measles remains endemic worldwide, despite current vaccination recommendations, and is associated with high morbidity and mortality rates. We describe all cases hospitalized in Bordeaux University Hospital (BUH), the starting point of a national significant measles outbreak in 2017–2018. Methods In this retrospective study, we included all patients hospitalized in BUH from September 1, 2017, to May 31, 2018. Inclusion criteria were age >1 year, clinical symptoms, and biological confirmation by measles immunoglobulin M or measles reverse transcription polymerase chain reaction positivity. Results We included 171 patients. Most patients were immunocompetent; only 19% had preexisting medical histories. Most patients had rash and fever (97%), but some cases were atypical and difficult to diagnose. Köplik's spots were reported in 66 cases (38%). The most frequent biological markers were blood inflammation markers (96%) and lymphopenia (81%). Unexpectedly, we found hyponatremia (<135 mmol/L) in 40% of patients. We identified peaks in January and March, corresponding to 76 D8 genotypes and 28 B3 strains. The following complications were reported in 65 patients (38%): pneumonia, hepatitis, and keratitis; 10 had neurological symptoms. One patient had Guillain-Barré syndrome, and a young immunocompromised patient died from measles inclusion-body encephalitis. Most of the patients (80%) had not been correctly vaccinated, including 28 health care workers. Some patients (n = 43, 25%) developed measles despite having plasma IgG. These included 12 possible vaccination failure cases. Conclusions During the BUH outbreak, measles was often complicated and sometimes atypical. Vaccination coverage was dramatically insufficient. We also describe vaccination failure cases that must be better investigated. [ABSTRACT FROM AUTHOR]

Introduction: Vertical transmission of the hepatitis B virus (HBV) is higher in infants born to pregnant women with a higher HBV DNA viral load even if the infants complete both active and passive vaccination. Although antiviral treatment is recommended for pregnant women during the antenatal period to reduce the rate of vertical transmission, most of them decline treatment.Methods: A decision tree was made to evaluate the costs and benefits involved when pregnant women either agreed or declined to take antiviral treatment during the antenatal period. The cost-effectiveness price was arrived at by multiplying the reduced vertical transmission rate with expenses of future medical care associated with vertical transmission.Results: From an individual mother's perspective, it was not cost-effective to receive antenatal antiviral treatment given the observed medication price and transmission rate in Singapore. However, the health system asserts that the current price of antiviral treatment is already far below the cost-effectiveness level, even without the Ministry of Health subsidies. Additionally, the awareness and perception of pregnant women also impacted treatment decisions.Conclusion: By analysing the decision-making process, our result explained the current low uptake rates of antenatal antiviral treatment for HBV among pregnant women. We also concluded that from the health system's perspective, it was worth providing subsidies for perinatal antiviral treatment to prevent huge expenses generated in the future by chronic HBV complications. [ABSTRACT FROM AUTHOR]

Tick-borne encephalitis (TBE) vaccines are highly effective in preventing TBE and vaccine failures (VF) are rare events. In this study, we compared the age distribution of TBE cases and TBE VF in three endemic countries: Sweden, Southern Germany, and Latvia. While the age distribution of TBE cases was similar for those

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Background: Immune escape mutation is a major reason for vaccination failure in vertical transmission of hepatitis B virus (HBV). Objectives: The aim of the current study was to explore the characteristics of HBV S region gene in vertical transmission and the influence of mutations on vaccination failure in HBV S region gene. Methods: A total of nine mother-child pairs with chronic HBV were recruited in this study, and all of the children received the vaccine. Next-generation sequencing (NGS) was used to investigate the sequences of HBV S gene from the mother and children. Results: The analysis of the sequencing data showed that all mother-child pairs are genotype B and genotype C mixed infection and the dominant genotype did not change in vertical transmission, and the consensus sequences of mothers and children were highly similar. Furthermore, the diversity of most amino acid sites had a small difference between mothers and children, and the mutations shared by mothers and children made up a high proportion of children's mutations; the rate was 83.13% -- 8.45%. Also, the research found many mutations that could cause immune escape in major hydrophilic region. Especially in "a" determinant, sC137S or sC139Y, which had an important influence on the structure of "a" determinant, were observed in all mother-child pairs. Conclusions: All the above results indicated that HBV S gene was highly conserved in vertical transmission, and these immune escape mutations that pre-exist in mothers were transmitted to children and resulted in vaccination failure. [ABSTRACT FROM AUTHOR]

Vaccination is an effective means to prevent infectious diseases including tick-borne encephalitis (TBE), an emerging Flavivirus infection. There is, however, only limited knowledge about risk of vaccination failure, the disease course and the challenges for work-up and care. Of note, there is evidence that patients with breakthrough disease experience a more severe disease course. We report the case of a previously healthy 49-year-old woman who developed severe myeloradiculitis caused by the TBE virus despite receiving a complete cycle of primary immunization and booster vaccinations within the recommended timeframe. The disease course was characterized by progressive tetraparesis, pain and bladder dysfunction and necessitated intensive care unit admission (ICU) and the escalation of pain management. This case raises awareness for the recognition of breakthrough disease in younger patients and reinforces the need to develop measures to identify patients with insufficient protection.

A mass vaccination campaign in India seeks to control and eventually eradicate foot-and-mouth disease (FMD). Biosanitary measures along with FMD monitoring are being conducted along with vaccination. The implementation of the FMD control program has drastically reduced the incidence of FMD. However, cases are still reported, even in regions where vaccination is carried out regularly. Control of FMD outbreaks is difficult when the virus remains in circulation in the vaccinated population. Various FMD risk factors have been identified that are responsible for FMD in vaccinated areas. The factors are discussed along with strategies to address these challenges. The current chemically inactivated trivalent vaccine formulation containing strains of serotype O, A, and Asia 1 has limitations including thermolability and induction of only short-term immunity. Advantages and disadvantages of several new-generation alternate vaccine formulations are discussed. It is unfeasible to study every incidence of FMD in vaccinated animals/areas in such a big country as India with its huge livestock population. However, at the same time, it is absolutely necessary to identify the precise reason for vaccination failure. Failure to vaccinate is one reason for the occurrence of FMD in vaccinated areas. FMD epidemiology, emerging and re-emerging virus strains, and serological status over the past 10 years are discussed to understand the impact of vaccination and incidences of vaccination failure in India. Other factors that are important in vaccination failure that we discuss include disrupted herd immunity, health status of animals, FMD carrier status, and FMD prevalence in other species. Recommendations to boost the search of alternate vaccine formulation, strengthen the veterinary infrastructure, bolster the real-time monitoring of FMD, as well as a detailed investigation and documentation of every case of vaccination failure are provided with the goal of refining the control program.

Pertussis vaccines have been effective at reducing pertussis-associated morbidity and mortality. However, they have a complex array of limitations, particularly associated with the duration of protection against clinical disease and imperfect immunity (carriage and transmission). Little is known about risk factors for pertussis vaccination failure. Understanding pertussis vaccination failure risk is most important in the paediatric population. This study aims to investigate risk factors for pertussis vaccination failure in (1) infants between birth and six weeks of age born to mothers who received pertussis booster vaccinations during pregnancy and (2) infants after the completion of the primary series (approximately five months old) to four years old. This will be achieved in a two-step process for each study group. Pertussis vaccination failure cases will first be described using a case series study design, relevant case characteristics will be sourced from six national administrative datasets. The case series study results will help select candidate risk factors (hypothesis generating step) to be tested in the retrospective cohort study (hypothesis testing step). Pattern analysis will be used to investigate risk factor patterns in the cohort study. The identification of higher risk groups enables targeting strategies, such as additional doses, to better prevent pertussis disease.

Porcine epidemic diarrhea virus (PEDV) causes devastating impact on global pig-breeding industry and current vaccines have become not effective against the circulating PEDV variants since 2011. During the up-to-date investigation of PEDV prevalence in Fujian China 2016, PEDV was identified in vaccinated pig farms suffering severe diarrhea while other common diarrhea-associated pathogens were not detected. Complete genomes of two PEDV representatives (XM1-2 and XM2-4) were determined. Genomic comparison showed that these two viruses share the highest nucleotide identities (99.10% and 98.79%) with the 2011 ZMDZY strain, but only 96.65% and 96.50% nucleotide identities with the attenuated CV777 strain. Amino acid alignment of spike (S) proteins indicated that they have the similar mutation, insertion and deletion pattern as other Chinese PEDV variants but also contain several unique substitutions. Phylogenetic analysis showed that 2016 PEDV variants belong to the cluster of recombination strains but form a new branch. Recombination detection suggested that both XM1-2 and XM2-4 are inter-subgroup recombinants with breakpoints within ORF1b. Remarkably, the natural recombinant HNQX-3 isolate serves as a parental virus for both natural recombinants identified in this study. This up-to-date investigation provides the direct evidence that natural recombinants may serve as parental viruses to generate recombined PEDV progenies that are probably associated with the vaccination failure. [ABSTRACT FROM AUTHOR]

Canine parvovirus (CPV) is a highly contagious and worldwide cause of serious and often fatal disease in dogs, despite the widespread availability of vaccines. Which vaccine-related factors are associated with vaccination failure is largely unknown, and there are no reports from Australia. In this study – the first national population-level CPV study of its kind ever conducted – we analysed data on 594 cases of apparent CPV vaccination failure reported from an Australian national surveillance system to determine whether vaccine strain, type or administration protocol are risk factors for vaccination failures. The strain of CPV used in vaccine manufacture was not significantly associated with vaccination failure in clinical practice. The vaccine type (killed versus attenuated vaccine) for puppies diagnosed with CPV was associated with a lower mean age at time of vaccination (P = 0.0495). The age at administration of the last CPV vaccination a puppy received prior to presenting with disease was a significant (P = 0.0334) risk factor for vaccination failure, irrespective of whether the vaccine was marketed for a 10-week or 12-week or greater vaccination finish protocol. There was also a strong negative correlation between age at last vaccination prior to disease and vaccination failure (P < 0.0001): the later a puppy received this last vaccination, the lower the risk of vaccination failure. This supports the hypothesis that the use of final vaccination in puppies at less than 16 weeks of age predisposes to vaccination failure and warrants a final age for vaccination recommendation to be at least 16 weeks for all canine parvovirus vaccines, especially in outbreak situations. The large number of cases identified in this study confirms that CPV vaccination failure is occurring in Australia. Veterinarians should consider CPV as a differential diagnosis in cases with appropriate clinical presentation, regardless of the reported vaccination status of the dog. [ABSTRACT FROM AUTHOR]

Marek's disease (MD) virus (MDV) has been evolving continuously, leading to increasing vaccination failure. Here, the MDV field strain BS/15 was isolated from a severely diseased Chinese chicken flock previously vaccinated with CVI988. To explore the causes of vaccination failure, specific-pathogen free (SPF) chickens vaccinated with CVI988 or 814 and unvaccinated controls were challenged with either BS/15 or the reference strain Md5. Both strains induced MD lesions in unvaccinated chickens with similar mortality rates of 85.7% and 80.0% during the experimental period, respectively. However, unvaccinated chickens inoculated with BS/15 exhibited a higher tumor development rate (64.3% vs. 40.0%), but prolonged survival and diminished immune defects compared to Md5-challenged counterparts. These results suggest that BS/15 and Md5 show a similar virulence but manifest with different pathogenic characteristics. Moreover, the protective indices of CVI988 and 814 were 33.3 and 66.7 for BS/15, and 92.9 and 100 for Md5, respectively, indicating that neither vaccine could provide efficient protection against BS/15. Taken together, these data suggest that MD vaccination failure is probably due to the existence of variant MDV strains with known virulence and unexpected vaccine resistance. Our findings should be helpful for understanding the pathogenicity and evolution of MDV strains prevalent in China. [ABSTRACT FROM AUTHOR]

Background: Vaccination of poultry to control highly pathogenic avian influenza virus (HPAIV) H5N1 is used in several countries. HPAIV H5N1 of clade 2.2.1 which is endemic in Egypt has diversified into two genetic clades. Clade 2.2.1.1 represents antigenic drift variants in vaccinated commercial poultry while clade 2.2.1.2 variants are detected in humans and backyard poultry. Little is known about H5N1 infection in vaccinated turkeys under field conditions. Case presentation: Here, we describe an HPAI H5N1 outbreak in a vaccinated meat-turkey flock in Egypt. Birds were vaccinated with inactivated H5N2 and H5N1 vaccines at 8 and 34 days of age, respectively. At 72nd day of age (38 days post last vaccination), turkeys exhibited mild respiratory signs, cyanosis of snood and severe congestion of the internal organs. Survivors had a reduction in feed consumption and body gain. A mortality of ~29% cumulated within 10 days after the onset of clinical signs. Laboratory diagnosis using RT-qPCRs revealed presence of H5N1 but was negative for H7 and H9 subtypes. A substantial antigenic drift against different serum samples from clade 2.2.1.1 and clade 2.3.4.4 was observed. Based on full genome sequence analysis the virus belonged to clade 2.2.1.2 but clustered with recent H5N1 viruses from 2015 in poultry in Israel, Gaza and Egypt in a novel subclade designated here 2.2.1.2a which is distinct from 2014/2015 2.2.1.2 viruses. These viruses possess 2.2.1.2 clade-specific genetic signatures and also mutations in the HA similar to those in clade 2.2.1.1 that enabled evasion from humoral immune response. Taken together, this manuscript describes a recent HPAI H5N1 outbreak in vaccinated meat-turkeys in Egypt after infection with a virus representing novel distinct 2.2.1.2a subclade. Conclusions: Infection with HPAIV H5N1 in commercial turkeys resulted in significant morbidity and mortality despite of vaccination using H5 vaccines. The isolated virus showed antigenic drift and clustered in a novel cluster designated here 2.2.1.2a related to viruses in poultry in Israel, Gaza and Egypt. Enforcement of biosecurity and constant update of vaccine virus strains may be helpful to protect vaccinated birds and prevent spillover infection to neighbouring countries. [ABSTRACT FROM AUTHOR]

Background: SARS-CoV-2 immunogenicity in patients with gastrointestinal cancer (GI cancer) following second and third vaccination was analyzed., Methods: A total of 125 patients under active anticancer therapy or in follow-up care were included in this prospective study. Seroprevalence of SARS-CoV-2 anti-spike and surrogate neutralization antibodies (NABs) was measured., Results: Four weeks after second vaccination, adequate titers of SARS-CoV-2 anti-spike immunoglobulin G (IgG) [≥282.0 binding antibody units (BAU)/mL] were found in 62.2% of patients under treatment versus 96.3% of patients in follow-up care (P<0.01). Sufficient titers of SARS-CoV-2 surrogate NAB (≥85.0%) were found in 32.7% of patients under treatment versus 70.6% in follow-up care (P<0.01). Titers of SARS-CoV-2 anti-spike IgG were especially low in patients with colorectal cancer (CRC). For SARS-CoV-2 surrogate NAB, patients with hepatocellular carcinoma (HCC) and with pancreaticobiliary cancer showed the lowest titers (P<0.01). SARS-CoV-2 anti-spike IgG and SARS-CoV-2 surrogate NAB were associated with a correlation coefficient of 0.93. Reaching a titer of SARS-CoV-2 anti-spike IgG ≥482.0 BAU/mL, protective levels of SARS-CoV-2 surrogate NAB (≥85.0%) could be assumed. Following booster vaccination, all patients reached effective antibody titers., Conclusions: Patients with active GI cancer showed impaired immunogenicity after second SARS-CoV-2 vaccination which was overcome by booster vaccination. Our findings were tumor-related and pronounced in patients with CRC and HCC. Waning immunity over time and antibody escape phenomena by variant of concern Omicron must be considered in these especially vulnerable patients., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-22-1065/coif). MBM received consulting fees; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events; and support for attending meetings and/or travel from Gilead, Pfizer and Virology Education. CB received grants or contracts from any entity; consulting fees; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events; and support for attending meetings and/or travel; from DZIF, Hector Foundation, DFG, NEAT ID, AbbVie, Gilead JnJ, MSD and ViiV. He participated on a Data Safety Monitoring Board or Advisory Board; and was leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid (Mavmet Study, DAIG, EACS). GJR received travel expenses and honoraria from Gilead. SS received grants or contracts from any entity; and support for attending meetings and/or travel from German Center for Infection Research, DFG, Gilead, Abbvie and Johnson&Johnson. He holds stock or stock options (MIG9 Fonds containing BionTech). MAGC has contributed to advisory boards for Roche, Eisai. BMS, MSD and AZ. The other authors have no conflicts of interest to declare., (2023 Journal of Gastrointestinal Oncology. All rights reserved.)

Background. Hepatitis B vaccination has proven to be very safe and highly effective. This study assessed the proportion of successfully vaccinated individuals among cases with acute hepatitis B, the proportion of preventable cases if individuals were vaccinated as recommended, and the reasons for failures. Methods. We analyzed data reported to the Italian Surveillance System for Acute Viral Hepatitis from 1993 to 2014. Results. A total of 362 of 11 311 (3.2%) cases with acute hepatitis B were vaccinated. Of the 277 cases for whom immunization data were available, 50 (18%) received a complete vaccination course according to the correct schedule and before exposure to hepatitis B virus. Molecular characterization of 17 of these cases showed that 6 were infected with S-gene mutants. Among the 10 949 unvaccinated cases, 213 (1.9%) escaped mandatory vaccination and 2821 (25.8%) were not vaccinated despite being at increased risk of infection. Among the latter, the most common risk factors were cohabitation with hepatitis B surface antigen (HBsAg) carriers, intravenous drug use, and homosexual/bisexual practices. Thirty-seven percent of the unvaccinated households with HBsAg carriers were aware of their risk. Lack of trust in the vaccination, negative attitude, and inaccurate beliefs followed by lack of or poor communication and low perceived severity of the disease were the most frequent reasons for vaccine hesitancy. Conclusions. Development of acute disease in successfully vaccinated individuals is a rare event. Further efforts are needed to enhance the vaccine coverage rate in individuals at increased risk of infection. [ABSTRACT FROM AUTHOR]

Background: HBV Pre-S/S gene mutations can occur before or after implementation of combined vaccination program. HBV Prs-S/S gene mutation is a risk factor of vaccination failure and frequently causes HBV vertical transfection. Objectives: To assess the association of hepatitis B virus (HBV) S gene mutations with vertical transmission. Patients and Methods: In this prospective nested case-control study, a total of 60 pregnant women with positive serum HBsAg and HBV DNA > 107 IU/mL were divided into a case group (15 cases with vaccination failure) and a control group (45 cases with vaccination success) according to whether their infants tested positive for HBV infection. Mothers and their children in the case group were further sub-divided into groups including mothers, newborns and infant (the same newborns at age of seven months). The pre-S/S gene mutations were detected by PCR and sequenced and its association with vertical transmission of HBV was analyzed. Results: HBV genotype B was the dominant genotype in the both groups' mothers. Each mother-child pair in case group had the same HBV genotype. There were no significant differences in mutation frequencies of HBV Pre-S/S gene between case and control groups' mothers (Fragment 1(M): 2 vs. 4, P> 0.05; Fragment 2 (M): 10 vs. 10, P> 0.05), or among the mothers, newborns and infants in the case group (Fragment 1 (M): 2, 2, and 3, respectively, P > 0.05; Fragment 2 (M): 10,10 and 10 respectively, P > 0.05). Mutation site analysis of the both groups' mothers demonstrated 108 different mutation sites in the HBV pre-S/S gene, with 105 silent mutations and 5 mis-sense mutations including ntA826G, ntC531T, ntT667C, ntC512T and ntC546A. Among 15 mother-newborn-infant pairs with successful PCR and sequence in case group, 7 (41.17%) mother-newborn pairs, 9 (60.00%) mother-infant pairs and 3 (20.00%) infant-newborn pairs had different mutation sites. Conclusions: HBV in children due to vaccination failure was resulted from vertical transmission. HBV Pre-S/S gene mutations were prevalent and could occur before or after vaccination. Therefore, simply analyzing mutation frequency of HBV gene was not of value. To advance blocking HBV vertical transmission, future studies should focus on specific mutation sites, potentially associated with vaccination failure. [ABSTRACT FROM AUTHOR]

Introduction: Increased mortality was observed in a multi-aged flock of Village Chicken farm. The clinical signs observed among the chicken includes depressed, weak, diarrhoea and low in flock uniformity. Results: The clinical signs, post mortem findings and bacteriology result suggestive of fowl cholera which is caused by Pasteurella multocidu. Post mortem findings showed high incidence of multifocal pin-point white spot lesions on the surface of the liver, petechial haemorrhage on the epicardial fatty tissue of the heart and also congested lungs. Conclusion: The bacteriology result confirmed the presence of P. multocidu in the chicken. Vaccination failure, poor management and biosecurity were among the cause of reoccurrence of fowl cholera in this farm. [ABSTRACT FROM AUTHOR]

From 2008 to 2013, sample sets from 534 patients displaying clinical symptoms of mumps were submitted to the German Reference Centre for Measles, Mumps and Rubella. Mumps virus infection was confirmed in 216 cases (40%) by PCR and/or serology. Confirmed cases were more frequently seen in male than in female patients (128 vs. 81); the age group predominantly affected was 15 to 29 years old (65%, median age: 26.4 years). The majority of the confirmed cases had a remote history of vaccination with one or two doses of a mumps-containing vaccine (69%). Our results indicate that mumps virus caused two outbreaks in Bavaria in 2008 and 2010/2011 and a third one in Lower Saxony in 2011. Mumps virus genotype G was preponderantly detected from 2008 to 2013. For 107 of the 216 patients with a confirmed mumps infection, we correlated the results from PCR and serology. PCR detected cases during the first week after onset of symptoms (74% positive results). PCR worked best with throat swabs and oral fluids (61% and 60% positive results, respectively). IgM was more reliable with a longer time after onset of symptoms (67%), but indirect IgM serology was of insufficient sensitivity for vaccinated mumps cases (30%); the IgM μ-capture assay detected more cases in this group. Mumps virus is able to initiate an infection in vaccinated patients (secondary vaccine failure, SVF) although it is unclear to what extent. Since SVF does occur in highly vaccinated populations and IgM will not increase to detectable levels in all SVF patients, we strongly recommend using PCR plus serology tests to avoid false-negative diagnoses in vaccinated individuals with clinical signs of mumps. [ABSTRACT FROM AUTHOR]

PCV2 can be divided into three different genotypes: PCV2a, PCV2b and PCV2c. Since 2004/2005 PCV2b has become the predominant genotype in the domestic pig population worldwide. In the years 2010 and 2012 PCV2b mutant strains (mPCV2), classified as PCV2b-1C strains, were detected in porcine circovirus diseases (PCVD) affected pigs in China and the United States, respectively. Within one year (April 2013–April 2014) newly emerging mPCV2 strains were isolated in seven German pig farms routinely vaccinating against PCV2. Histopathological, clinical and molecular biological findings including in-situ hybridization (ISH) and real-time PCR indicate PCVD in the affected animals. Characterized isolates from five farms were closely related to the PCV2b-1C reference strain BDH (GenBank no. HM038017 ), whereas strains from two other farms were only 99.1% and 99.0% identical (based on the nucleotide sequence of the complete genome) to mPCV2 strain BDH, respectively. [ABSTRACT FROM AUTHOR]

Foot-and-mouth disease virus (FMDV) serotypes O, A and Asia1 are responsible for significant number of disease outbreaks in Bangladesh; however serotype Asia1 has not been reported in circulation since 1996. The present investigation reports the detection of serotype FMDV Asia1 from local farms in 2012 and 2013 outbreaks. The farms were located in Jessore and Gazipur districts, and one of these farms was under vaccine control programme. Phylogenetic analysis of the complete VP1 gene revealed that FMDV Asia1 is under genetic lineage C having close similarity to the Asia1 sequences of Indian origin. The circulatory genotype Asia1 showed VP1 protein sequence heterogeneity of eight amino acid substitutions within the G-H loop with the vaccine strain [IND 63/72 (AY304994)] used in vaccination programme. ELISA assay revealed that, of seven, only one local field serum sample (cattle vaccinated 38 days earlier) was positive at a titre level of >2·4 (log10) but failed to protect the cattle from infection occurred by the virus. This investigation focused that the eight amino acid substitution in VP1 protein at G-H loop of the locally circulated FMDV serotype Asia1 strain may be a reason for current vaccination failure. Significance and Impact of the Study This study presents the first report of the re-emergence of foot-and-mouth disease virus (FMDV) serotype Asia1 in Bangladesh after 1996. Bangladesh loses as much as US$125 million annually due to FMD. Vaccination is one of the effective strategies to prevent FMDV infection, and in Bangladesh, this practice is carried out in limited scale by imported vaccines. Vaccination failure has occurred due to the imported vaccine consist of FMDV strain(s) of different genetic lineage than locally circulated FMDV type Asia1. So this study encourages the local vaccine development targeting local circulatory FMD virus. [ABSTRACT FROM AUTHOR]

Non-responsiveness to conventional hepatitis B vaccines in individuals at high risk of exposure to hepatitis B virus (HBV) is an important public health problem and of particular relevance in health care providers. Yeast-derived conventional HBsAg vaccines fail to induce protective antibody titers in up to 10% of immune competent vaccinees. Therefore, a third generation HBV vaccine, Sci-B-Vac™, was developed which contains in addition to the small S antigen the PreS1 and PreS2 antigens. This vaccine proved to induce a highly potent cellular and humoral immune response in healthy individuals as well as protective antibody levels in non- and low-responders to conventional HBV vaccines. The aim of the study was to examine whether Sci-B-Vac™ triggers cellular and humoral immunity in individuals who failed immunization with conventional vaccines. We immunized 21 volunteers (15 non- and 6 low-responders) according to the standard vaccination schedule (0, 4 and 24 weeks), determined the cellular immunity by proliferation assay and interferon (IFN)-γ ELISpot and measured the anti-HBs antibody titers prior to each vaccination and four weeks after the third vaccine dose. Following three vaccinations, PreS/S-specific T-cell proliferation was detected in 8 out of 15 non-responders and 5 out of 6 low-responders. Specific IFN-γ responses were measured in 2 out of 15 non-responders and 4 out of 6 low-responders. All but one (20/21) study participants developed anti-HBs titers ≥10 IU/l after three vaccinations. Anti-HBs ≥100 IU/L were detected in 12 out of 15 non-responders and in 6 out of 6 low-responders. Anti-HBs ≥10 IU/l and <100 IU/l were found in 2 non-responders. These results indicate that Sci-B-Vac™ induces cellular immunity as well as protective anti-HBs antibody titers in non- and low-responders. In conclusion, these results confirm that Sci-B-Vac™ should be administered to non-responders to conventional HBV vaccines and patients with impaired immune function. [ABSTRACT FROM AUTHOR]

Abstract: Vaccination of cats against feline panleukopenia virus (FPV) has been a routine part of feline medicine for the past 40 or more years, and many of the same vaccines that were first developed in the 1960s are still in routine use today. However, there has been significant evolution of the virus in the last 40 years, in particular the emergence of canine parvovirus (CPV) in dogs in the late 1970s, which was a host range variant of the FPV-like virus, and the world-wide spread of the CPV-derived viruses since 1978. FPV and the various antigenic types of CPV have been isolated from cats, raccoons, and many different wild and captive carnivores. The consequences of these changes in the viral populations have not been investigated, and the effectiveness of the current vaccine protocols have not been reported. Here we review the recent findings about the evolution of the viruses in carnivores including cats, and describe a study that looks at the efficiency of vaccination of kittens using the standard protocols, which shows that many cats are not protected by those approaches. [Copyright &y& Elsevier]

Abstract: Despite remarkable success of immunization programmes on a global perspective, vaccines are neither 100% efficacious nor 100% effective. Therefore, vaccination failure, i.e. occurrence of a specific disease in an individual despite previous vaccination, may occur. Vaccination failure may be due to actual vaccine failure or failure to vaccinate appropriately. Universally accepted concepts and definitions of vaccination failure are required to assess and compare the benefit of vaccines used in populations. Here we propose general definitions for types of vaccination failure. In the future, these should be complemented by specific definitions for specific vaccines as needed depending on public health considerations. [Copyright &y& Elsevier]

Background: Uninterrupted transmission of highly pathogenic avian influenza virus (HPAIV) H5N1 of clade 2.2.1 in Egypt since 2006 resulted in establishment of two main genetic clusters. The 2.2.1/C group where all recent human and majority of backyard origin viruses clustered together, meanwhile the majority of viruses derived from vaccinated poultry in commercial farms grouped in 2.2.1.1 clade. Findings: In the present investigation, an HPAIV H5N1 was isolated from twenty weeks old layers chickens that were vaccinated with a homologous H5N1 vaccine at 1, 7 and 16 weeks old. At twenty weeks of age, birds showed cyanosis of comb and wattle, decrease in egg production and up to 27% mortality. Examined serum samples showed low antibody titer in HI test (Log2 3.2± 4.2). The hemagglutinin (HA) and neuraminidase (NA) genes of the isolated virus were closely related to viruses in 2.2.1/C group isolated from poultry in live bird market (LBM) and backyards or from infected people. Conspicuous mutations in the HA and NA genes including a deletion within the receptor binding domain in the HA globular head region were observed. Conclusions: Despite repeated vaccination of layer chickens using a homologous H5N1 vaccine, infection with HPAIV H5N1 resulted in significant morbidity and mortality. In endemic countries like Egypt, rigorous control measures including enforcement of biosecurity, culling of infected birds and constant update of vaccine virus strains are highly required to prevent circulation of HPAIV H5N1 between backyard birds, commercial poultry, LBM and humans. [ABSTRACT FROM AUTHOR]

Background: Individuals who reach the antibody threshold level of 10IU/l against the surface protein of the hepatitis B virus (HBV) after completion of a series of hepatitis B vaccination are considered to be long-term protected against a clinically manifest HBV infection. Case report: Here we describe an acute hepatitis B infection in a patient who received five hepatitis B vaccinations. Although his initial response to vaccination was moderate, he finally reached an excellent hepatitis B surface antibody level (anti-HBs) titres of more than 1000 IU/l in response to a booster vaccination with a recombinant DNA vaccine. Nevertheless, he developed full-blown acute hepatitis due to an HBV infection 14years after this booster vaccination. A DNA analysis of the surface protein encoding region followed by phylogenetic analysis showed that our patient was infected with a normal HBV strain that is circulating among men who have sex with men. To our knowledge, this is the first report of a genuine hepatitis B vaccination failure in someone who acquired a high anti-HBs level in response to a recombinant DNA hepatitis B vaccine. Conclusion: Healthcare workers whose response to the initial hepatitis B vaccination is moderate might be vulnerable to hepatitis B virus infection. [Copyright &y& Elsevier]

Abstract: Conventional hepatitis B vaccines do not elicit adequate antibody production in 5–10% vaccinees. This trial tests the ability of a third-generation vaccine, containing PreS1 and PreS2 antigens in addition to the S antigen, to elicit seroprotective titres in documented non- and low-responders, compared with those to a conventional vaccine. In the primary population of non-responders (<10IU/l anti-HBs antibodies after ≥4 previous injections of conventional vaccine) an enhanced antibody response was seen to additional injections of the third-generation vaccine compared with a conventional vaccine (absolute difference 14.9%; P =0.006). Enhanced antibody responses were also found in a population that included low responders. [Copyright &y& Elsevier]

Tick-borne encephalitis (TBE) vaccines are highly effective in preventing TBE and vaccine failures (VF) are rare events. In this study, we compared the age distribution of TBE cases and TBE VF in three endemic countries: Sweden, Southern Germany, and Latvia. While the age distribution of TBE cases was similar for those <50 years versus those ≥50 years in all three countries, in Sweden, a higher proportion of VF cases was ≥50 years, whereas most VF cases in Latvia were <50 years of age and more evenly distributed between those <50 years versus those ≥50 in Southern Germany. Here, theoretical explanations were provided, including differences in diagnostic practices, vaccine uptake between age groups, behavioral patterns and underlying medical conditions, as to why VF were generally older in Sweden than the other countries. There is no scientific rationale to give an extra priming dose of TBE vaccine to subjects ≥50 years of age. [ABSTRACT FROM AUTHOR]

• Less responsible behavior can be a consequence of vaccination failure. • The impact of vaccine efficacy on an infection propagation is examined. • The lower the vaccine efficacy, the more the epidemic can worsen. • Vaccinated people should not relax their protection measures. Vaccines do save lives; however, no vaccine provides complete immunity for all vaccinated individuals. Thus, some individuals remain susceptible to the contagious disease against which they were vaccinated. By relying on the supposed acquired immunity, these individuals can reduce the self-imposed prevention measures and, as a consequence, they can involuntarily promote the spread of the infection. Here, such individuals are taken into account in an epidemic model based on ordinary differential equations. Depending on the parameter values related to contagion and vaccine efficacy, a less responsible behavior post-vaccination can increase the basic reproduction number of the disease as compared to the case with no vaccine. This result is discussed by considering the current COVID-19 outbreak. [ABSTRACT FROM AUTHOR]