Vaccine Failure Research Articles

Development of a genotype-matched Newcastle disease DNA vaccine candidate adjuvanted with IL-28b for the control of targeted velogenic strains of Newcastle disease virus in Africa

Newcastle disease virus (NDV) is an extremely contagious and deadly virus that affects numerous bird species, posing serious threats to poultry production on a global scale. In addition to implementing biosecurity practices in farming systems, vaccination remains the most effective means of controlling Newcastle disease (ND). However, while existing commercial vaccines provide some level of protection, the effectiveness of these vaccines can be questionable, particularly in field settings where the complexity of vaccination program implementation poses significant challenges, especially against virulent genotypes of NDV. A genotype-matched NDV DNA vaccine could potentially offer a more effective vaccination approach than currently available live attenuated vaccines. By being specifically tailored to match circulating strains, such a vaccine might improve efficacy and reduce the risk of vaccine failure due to genotype mismatch. To develop an alternative vaccine approach, two ND DNA vaccines were constructed in this study. Each vaccine developed in this study contains the fusion (F) and haemagglutinin-neuraminidase (HN) genes of a virulent NDV genotype VII isolate from Tanzania. Interferon lambda-3 (IFNλ3; IL-28b), which has demonstrated capacity to significantly enhance specific adaptive immune responses and decreased levels of inflammatory cytokines, as well as improved protective responses at a high viral challenge dose, was included in one of the developed vaccines. These plasmids were designated pTwist-F-HN-VII-IL28b and pTwist-F-HN-VII. The two plasmids differed in that pTwist-F-HN-VII-IL28b contained the cytokine adjuvant IL-28b. Transfection of cells and subsequent immunofluorescence assays indicated that both plasmids expressed high levels of NDV F-HN proteins. In vivo immunization demonstrated that chicks intramuscularly immunized with pTwist-F-HN-VII-IL28b exhibited significant immune responses compared to chicks immunized with pTwist-F-HN-VII or the commonly used LaSota vaccine (LaSota), which was used as a control. The protective efficacy of pTwist-F-HN-VII-IL28b was 80% after challenge with the highly virulent NDV strain ON148423, compared to 60% for chicks vaccinated using LaSota, and pTwist-F-HN-VII. The findings of this study indicate that IL-28b can be employed as a molecular adjuvant for NDV vaccines. This study represents a key milestone in Newcastle disease vaccine research, particularly in the development of a genotype-matched DNA vaccine candidate. Additionally, this study demonstrated that the combination of F, HN, and IL-28b elicits an efficacious immune response against virulent NDV strains.

Measles secondary vaccine failure in a childcare setting: an outbreak report.

The Sunshine Coast Public Health Unit (SCPHU) identified a measles case in a childcare educator (CE) with secondary vaccine failure (SVF). The CE had been exposed to a confirmed measles case in a hospital emergency department and later developed symptoms including fever, cough, malaise, and a rash. Diagnostic tests confirmed measles virus infection. Sunshine Coast Public Health Unit (SCPHU) implemented control measures including contact tracing, vaccination, post-exposure prophylaxis, and quarantine for susceptible contacts. Out of 372 identified contacts, 72 were identified as susceptible, all of whom were infants and children. Despite the CE having close contact to all susceptible infants and children, no onward transmission occurred. This suggests that SVF cases pose a lower risk of spreading measles compared to immunologically naïve individuals. This report highlights the importance of prioritising immunologically naïve cases in outbreak responses.

Assessment of the humoral immunity against diphtheria, tetanus, and hepatitis B among children with acute lymphocytic leukemia

Background: Approximately all systemic therapies for childhood affect the immune system. The behavior of the immune system in leukemia patients following chemotherapy is not yet clearly defined. The probability of vaccination failure and the need for revaccination remain challenging for these patients. Aim: To evaluate the humoral immunity against diphtheria, tetanus, and hepatitis B in children with acute lymphocytic leukemia (ALL) immediately and 6 months after chemotherapy. Materials and Methods: In the present prospective cohort study, 21 patients with ALL referred to Mofid Children’s Hospital were studied immediately and 6 months after chemotherapy. Serum samples were collected from patients, and the levels of immunoglobulins (IgG, IgM, IgE, and IgA) antibodies against diphtheria, tetanus, and hepatitis B were determined using specific enzymelinked immunosorbent assay kits. The obtained data were analyzed using Statistical Package for Social Sciences 21 software. Results: A total of 13 males and 8 females with an average age of 8.6 ± 2.5 years were included in the present study. Six months after chemotherapy, the mean level of IgG, IgM, IgE, and IgA displayed an increase of 563.1 units in IgG, 11 units in IgM, 11.3 units in IgE, and 5 units in IgA levels. Moreover, data revealed that 6 months after chemotherapy, the mean level of IgG antibodies displayed an increase of 7.09, 3.43, and 1.03 units against hepatitis B, diphtheria, and tetanus, respectively. A significant relationship was found between the antibody level against diphtheria and the age group of the patients (p = 0.003). Conclusion: Humoral immune status was boosted after 6 months of chemotherapy, though all patients had some extent of lasting immune dysfunction. We indicate that survivors of childhood cancer have ongoing humoral immunological defects and may remain at risk for infectious complications after completion of therapy. Relevance for Patients: The present study indicated that systemic therapies for pediatrics with leukemia affect the immune system. Pediatrics with leukemia may remain at risk for infectious complications after completion of therapy.

Modeling and analysis of transmission dynamics of tuberculosis with preventive treatment and vaccination strategies in China

In China, approximately 350 million people with latent tuberculosis infection (LTBI) are the major source of new TB cases, meanwhile, BCG vaccination for newborns and children under five fails to fully arrest the TB epidemic due to the mechanisms of vaccine failure. It is expected that widespread TB preventive treatment (TPT) and new vaccination strategies may be solutions to end TB. This work allows for TPT and vaccination strategies in a nonlinear age-structured SVEIR model with nonexponential residence times to exploit the interventions for ending TB in China. Global stability analysis reveals that the target model preserves the threshold-value dynamics in terms of the basic reproduction number so that some existing results are extended, moreover, the model is applied to fit the data of TB cases in China. Furthermore, sensitivity analysis for endemic steady state suggests that four potentially feasible interventions (i.e., amplifying the inhibition effect of infectious individuals by limiting range of their mobility, shortening the treatment duration for patients, adopting BCG revaccination and enhancing the rate of TPT) can lower the steady level of infectious individuals at endemic steady state and delay its arrival time. Finally, several multifaceted strategies composed of these interventions are compared via emulational experiments. We conclude that the target of End TB Strategy by 2035 in China would be reached just by the multifaceted strategy with moderate intensity if BCG revaccination, the duration of TPT for 2 months and a 40% completion rate are realized. This investigation sheds light on the fantastic potential applications of new TPT and vaccination strategies.

Expression of Immunodominant gI Protein of Duck Enteritis Virus and its Evaluation for ELISA

Background: Duck plague (DP), also known as duck viral enteritis (DVE) caused by Anatid alpha herpesvirus-1, is the major infectious viral disease reported in India very often with significant economic losses due to high morbidity and mortality. The genome is approximately 158,091 bp with a genomic arrangement pattern (UL-IRS-US-TRS) that corresponds to type-D herpesvirus. The incubation period of the disease in domestic ducks ranges from 3 to 7 days and the mortality varies from 5-100%. It has been reported that the strategies to monitor and control DVE were often frustrating because the disease tends to establish a latent infection in waterfowl and vaccination failure. The present study was taken as an attempt to develop indirect ELISA using developed recombinant gI protein to diagnose DEV in field condition. Methods: In this study, we selected a membrane glycoprotein protein I (US7) gene, that plays an important role in virion sorting, cell-cell spread and binding of IgG Fc receptor. The gI protein was cloned with pET-32a (+) and expressed in a prokaryotic (E. coli) expression system. Further, recombinant protein was purified by nickel column affinity chromatography and refolded by dialysis. The obtained concentrated protein was then evaluated for its antigenicity and reliability in an Indirect-Enzyme-linked immunosorbent assay (ELISA) for DEV antibody detection in duck sera. Result: A panel of positive, negative and vaccinal serum was evaluated which indicated the potential use of the protein in the development of a serological assay for sero- surveillance of duck plague infection.

Vaccine Quality Challenges in Secretly Traded H5 and H9 Avian Influenza Vaccines in Nigeria

Avian Influenza Virus (AIV) especially the highly pathogenic subtype H5Nx causes Avian Influenza (AI) disease and it is a major threat to the poultry industry and public health worldwide. Vaccination is one of the control measures in many countries, though restricted in Nigeria. As such, some poultry farmers secretly employ imported H5 and H9 AI vaccines to vaccinate their chickens. This study investigated the antigenic quality of these imported vaccines. Four imported vaccine brands were tested using Hemagglutination (HA) test and Reverse Transcriptase Polymerase Chain Reaction (RTPCR). All four vaccine samples tested negative in the HA test, indicating a lack of detectable HA antigen titer. Similarly, RT-PCR failed to amplify the targeted region of the viral matrix gene in any of the vaccine samples against reference control. These negative results are of great concern and suggest that the imported H5 and H9 vaccines lack essential antigens that could stimulate antibodies. Thus, potentially rendering them ineffective against circulating AI subtypes. The failure in antigenic quality could be due to myriads of factors including improper storage, transport (often due to illegal import), or limitations in the original vaccine production process. Regardless of the specific cause, these findings highlight the potential risks associated with the use of unregulated vaccines. Poultry farmers who use these imported vaccines may be incurring unnecessary costs while receiving a false sense of security for their flocks. In conclusion, due to the apparent lack of efficacious antigens, we suggest a quality monitoring of imported H5 and H9 vaccines in Nigeria for compliance with local regulations on vaccine use, biosecurity measures and investigation into the root causes of the vaccine failure observed in this study.

Managing a 4000-participant cohort with a novel mobile app: data from the RisCoin study in Germany

Abstract Issue RisCoin, a prospective monocentric longitudinal observational study, aimed to identify risk factors for COVID-19 vaccine failure. Secondary aim is to monitor symptoms, SARS-CoV-2 infection, vaccination status of 3816 enrolled healthcare workers (HCW) and 180 patients with inflammatory bowel disease (IBD). Since the LMU University Hospital Munich served both as study sponsor and employer of the HCW, a secured approach was required. Description of the solution Participants accessed the study app (CentraXX, KAIROS GmbH, Germany) via pseudonymized Contact-ID with irreversible anonymization after 6 months. Key app features were the serological results report, bidirectional messaging, and weekly survey for self-reported data on vaccinations, infections, and symptoms. Active app use was defined as submitting >1 weekly survey during the study period 10.2021-12.2022. Results Over 15 months, our study team maintained 1964 two-way communications with 958 participants via the app. Of 3979 participants with app access, 3622 (91%) were active users, 2606 (65%) submitted 1 to 11 surveys, 1016 (26%) made ≥12 submissions (P75, “frequent users”). Frequent users were more likely to be IBD patients (p = 0.001), female (p < 0.001), aged 60 or older (p < 0.001). Staff in administration and nurses were more likely to be frequent users compared to physicians (p < 0.001). Main problems included the initial operational system disparities resulting in app crashes and continuous need for app reactivation. Both led to loss of active participants and required substantial staff resources to onboard and support participants during the study. Lessons The study app enabled secure, flexible, bidirectional communication with all participants. Despite technical issues, the majority actively used the app and provided valuable longitudinal data through weekly survey submissions. Key messages • A study-specific app provides a flexible and secure bidirectional anonymous communication for the study team and participants. • Adherence to app-based communication and data collection for pandemic monitoring was particularly high among patients, nurses and administrative staff.

Comparative Efficiency of Polyethylene Glycol, Ammonium Sulphate, Methanol Precipitation, and Ultrafiltration Techniques for the Down Streaming of Viral Antigen

Background: Foot and mouth disease (FMD) is ubiquitous worldwide but endemic in many countries of Africa, Asia, South America, and the Middle East. Many reasons contribute to the incidence of viral diseases even in vaccinated animals. These reasons include low antigenic payload, low PD50, improper formulation, unstable vaccine containing antigen, and genetically different from field strain. Among these, the most important one is the low antigenic load per dose of the vaccine. Vaccine failure is mainly due to the direct use of virus suspension in the vaccine without the concentration of viral antigen. Another reason to concentrate the antigen is small volume storage in the vaccine bank. These issues are mostly concerned with developing countries like Pakistan which lack antigen concentration technology. The concentration of the virus is a major milestone to be achieved for the production of an effective vaccine as well as for the diagnostic tool.Methods: Different techniques including precipitation with polyethylene glycol, ammonium sulfate, methanol, and filtration through an ultra-filter membrane were used for the concentration of viral suspension. Antigen quantification in terms of µg/ml was determined through size exclusion chromatography by using Sephacryl S-300 as a stationary phase.Results: Percentage recovery of FMDV calculated through analysis of chromatograms found 77.80%, 59.75%, 32.50%, and 13.83% for polyethylene glycol, ammonium sulfate, ultra-filtration, and methanol treated samples respectively.Conclusion: Classical polyethylene glycol precipitation showed a maximum percentage recovery of foot and mouth disease virus as compared to other concentration methods.Keywords: Foot and mouth disease virus (FMDV); Concentration Methods; Polyethylene Glycol (PEG); Size Exclusion Chromatography (SEC); Sephacryl S-300

Oral co-administration of Lactiplantibacillus plantarum 16 and Lacticaseibacillus rhamnosus P118 improves host defense against influenza A virus infection.

Influenza is an important zoonotic disease that persistently threatens global public health. While it is widely acknowledged that probiotics can modulate the host response to protect the host against infectious disease, the prophylactic efficacy on respiratory viral infection and the detailed mechanism remains elusive. Lactobacillus, the most commonly used probiotic widely applied in food production, has garnered significant attention. In our study utilizing both C57BL/6 and BALB/c mouse models, we explored the protective effect against two strains of influenza virus, A/Mink/China/01/2014(H9N2) and A/California/04/2009(H1N1), through the administration of Lactiplantibacillus plantarum strain 16 (L. plantarum 16) and Lacticaseibacillus rhamnosus strain P118 (L. rhamnosus P118), aiming to identify robust probiotic strains with antiviral properties. Our findings indicate that administering L. plantarum 16 or L. rhamnosus P118 alone does not provide sufficient protection against influenza. However, the co-administration of L. plantarum 16 and L. rhamnosus P118 dramatically reduces viral titers in the respiratory tract and lung, thereby markedly alleviating the clinical symptoms, improving prognosis, and reducing mortality. The mechanisms underlying this effect involve the modulation of host gut microbiota and metabolism through the co-administration of L. plantarum 16 and L. rhamnosus P118, resulting in enrichment of Firmicutes and enhancement of phenylalanine-related metabolism, ultimately leading to an augmentation of the antiviral immune response. Notably, we identified that the circulating metabolic molecule 2-Hydroxycinnamic acid plays a significant role in combating influenza. Our data suggest the potential utility of L. plantarum 16 and L. rhamnosus P118 two-bacterium or 2-Hydroxycinnamic acid in preventing influenza.IMPORTANCEVaccination represents the most optimal strategy to control influenza. Nevertheless, influenza viruses constantly evolve due to antigenic drift and shift, leading to the need for regular updates on influenza vaccines. Additionally, vaccination failure poses significant challenges to influenza prevention. Therefore, it is essential and beneficial to identify novel or universal antiviral measures to protect against influenza. While cumulative data suggest that probiotics offer protection against infectious diseases, the specific mechanisms, such as the effective metabolites or components, remain largely unknown. Our research discovered the capacity of combinational two-bacterium Lactiplantibacillus plantarum 16 and Lacticaseibacillus rhamnosus P118 to fight against influenza infection in a mouse model. The protection may occur through modulating the host's gut microbiota and metabolism, further influencing the host's antiviral immune response. Notably, we have identified a novel metabolic molecule, 2-Hydroxycinnamic acid, capable of enhancing antiviral response and restricting viral replication in vivo.

Emergence and etiological characteristics of novel genotype Ⅱ pseudorabies virus variant with high pathogenicity in Tianjin, China

Pseudorabies (PR) is a highly infectious disease caused by pseudorabies virus (PRV). This study aimed to detect and identify recent outbreaks of genotype Ⅱ PRV, and further analysis it's etiological characteristics and pathogenicity. The brain tissues with suspected PRV infection were isolated and the main virulence-related genes of the isolated PRV strain were amplified and sequenced for phylogenetic analysis. In addition, the pathogenicity of the isolated PRV strain to 6-week-old mice and 9-days-old suckling piglets were evaluated. The results showed that a PRV strain was successfully isolated and named PRV TJbd2023 strain, which could proliferate in PK-15 cells and TCID50 of the 6th generation virus reached 107.57/0.1 ml. Phylogenetic trees and amino acids analysis were constructed based on full-length gE sequences, which showed that PRV TJbd2023 strain was clustered into genetype Ⅱ PRV variant with a characteristic 21-nucleotide insertion (encoding 63AASTPAA69) in gC gene, and some amino acid point mutations were also found in other virulence-related genes, including gB protein R223H and E836K, gD protein R320S, and gE protein T242A. Animal experiments showed that TJbd2023 could cause acute neurological symptoms with 103.41/mL LD50 on KM mice, and intranasal inoculation of suckling piglets with 2 ml of TJbd2023 strain(106.57/0.1 ml) led to a mortality rate of 66.70 %. Emerging genotype Ⅱ PRV variant such as isolated in our research named TJbd2023 with high pathogenicity might be responsible for recent outbreaks of PRV and immunization failure of Bartha-K61 vaccine in Tianjin, China.

Detection of PCV2d in Vaccinated Pigs in Colombia and Prediction of Vaccine T Cell Epitope Coverage against Circulating Strains Using EpiCC Analysis.

Porcine circovirus type 2 (PCV2) is strongly linked to a group of syndromes referred to as porcine-circovirus-associated diseases (PCVADs), which are controlled through vaccination; however, this does not induce sterilizing immunity but is instead involved in the evolution of the virus and is considered a factor in vaccine failure. This study sampled 84 herds (167 pigs) vaccinated against PCV2 and with clinical signs of PCVADs in five provinces across Colombia. PCV2 was identified and further characterized at the molecular level via genotyping and phylogenetic reconstructions. In addition, PCV2-associated lesions were examined via histopathology. Furthermore, the PCV2-Cap sequences retrieved were compared with three vaccines via the EpiCC tool and T cell epitope coverage. The prevalence of PCV2 was 82% in pigs and 92.9% in herds. The highest viral loads were identified in lymphoid tissue, and PCV2d emerged as the most predominant in pigs and herds (93.4% and 92.3%). Sequences for PCV2-ORF2 (n = 57; 55 PCV2d and 2 PCV2a) were determined, and PCV2d sequences were highly similar. The most common pneumonia pattern was suppurative bronchopneumonia, while the most common lung lesion was exudation in the airways; in lymphoid tissue, there was lymphoid depletion. The bivalent vaccine (PCV2a and PCVb) exhibited a higher EpiCC score (8.36) and T cell epitope coverage (80.6%) than monovalent PCV2a vaccines. In conclusion, PCV2d currently circulates widely in Colombia. Despite vaccination, there are clinical cases of PCV2, and immunoinformatic analyses demonstrate that bivalent vaccines improved the average coverage.

The Effects of Vaccination Status and Age on Clinical Characteristics and Severity of Measles Cases in the United States in the Post-Elimination Era, 2001-2022.

Despite high vaccine-effectiveness, wild-type measles can occur in previously vaccinated persons. We compared the clinical presentation and disease severity of measles by vaccination status and age in the post-elimination era in the United States. We included U.S. measles cases reported from 2001-2022. Breakthrough measles was defined as cases with ≥1 documented dose of measles-containing vaccine, classic measles as the presence of rash, fever, and ≥1 symptoms (cough, coryza, or conjunctivitis), and severe disease as the presence of pneumonia, encephalitis, hospitalization, or death. Vaccinated cases with low and high avidity IgG were classified as primary (PVF) and secondary (SVF) vaccine failures, respectively. Among 4,056 confirmed measles cases, 2,799 (69%) were unvaccinated, 475 (12%) were breakthrough infections, and 782 (19%) had unknown vaccination; 1,526 (38%), 1,174 (29%), and 1,355 (33%) were aged <5, 5-19, and ≥20 years, respectively. We observed a general decline in classic presentation and severe disease with an increase in the number of doses, and less complications among children aged 5-19 years compared to other age-groups. Among 93 breakthrough cases with avidity results, 11 (12%) and 76 (82%) were classified as PVF and SVF, respectively, with a higher proportion of PVFs having a classic measles presentation and severe disease than SVFs. Breakthrough measles cases tended to have milder disease with less complications. A small proportion of breakthrough infections were due to PVF than SVF. It is critical to maintain high MMR vaccination coverage in the United States to prevent serious measles illnesses.

GROWTH RESPONSE AND ANTIVIRAL POTENTIALS OF NEEM (AZADIRACHTA INDICA J.) AND SCENT (OCIMUM SANCTUM L.) LEAF MEALS AGAINST NEWCASTLE AND INFECTIOUS BURSAL DISEASES IN BROILER CHICKS

Newcastle disease (ND) and infectious bursal disease (IBD) are the most feared viral disease of poultry. Viral reversion, vaccine failure, risk of autoimmune diseases and allergic disorder has led to the search for alternatives for vaccination. The effects of neem (Azadirachta indica) and scent (Ocimum santum) leaf meals fed singly or in combination on the growth performance and their antiviral potencies in broiler chicks were investigated. Two hundred 1-day old Ross 308 unsexed broiler chicks were randomly allotted to 5 treatments, consisting of 5 replicates with 8 birds each. Treatments 1 and 2 were basal diets with no leaf meals, treatments 3, 4 and 5 had the basal diets plus 3% neem leaf meal (NLM), 3% scent leaf meal (SLM) and the blend of 2% NLM + 2% SLM, respectively. Birds in treatments 2-5 were unvaccinated against Newcastle disease and Infectious bursal disease while birds in treatment 1 were vaccinated. Performance indices were measured on a weekly basis. At day-21, blood samples were randomly collected from 2 birds per replicate for haemagglutination inhibition and agar gel precipitation tests. Data were subjected to descriptive statistics and ANOVA at P&lt;0.05. Birds fed diets supplemented with a combination of 2% neem + 2% scent leaves had the highest weight gain (819.49g/b) and lowest feed conversion ratio (1.83). In conclusion, birds fed diets supplemented with 3% neem and 3% scent leaf meals singly had haemagglutination inhibition titre values and conferred immunity above protective threshold against Newcastle disease and produced antibodies against Infectious bursal disease.

Study of pediatric invasive pneumococcal disease in the 13-pneumococcal conjugated vaccine era

BackgroundInvasive pneumococcal disease (IPD) remains a significant concern among children under 5, despite vaccination efforts. This study assessed IPD prevalence and associated risks in pediatric population. MethodsAn observational, retrospective, multicenter study in Comunidad Valenciana, Spain, of IPD cases in children under 13 from January 2012 to September 2022. Data from the CV Microbiology Surveillance Network (RedMIVA) and medical records were reviewed. ResultsA total of 379 IPD cases in 377 patients were analyzed, predominantly males (54.11 %) under 5 (81.17 %). PCV13 vaccination notably reduced PCV13-serotypes IPD (p=0.0002), except serotype 3. Pneumonia was common, with half having underlying conditions (50.40 %). Worse outcomes occurred in patients with neurological disorders (ANOVA, p=0.57). Vaccine failures often involved underlying conditions (63 %) and serotypes 3 and 19A. Immunodeficiencies may relate to recurrent IPD, but evidence is limited. ConclusionDespite vaccination, IPD still impacts children, influenced by immunological status, affecting severity and mortality.

SARS-CoV-2 variant replacement constrains vaccine-specific viral diversification.

Coronavirus disease 2019 (COVID-19) vaccine breakthrough infections have been important for all circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant periods, but the contribution of vaccine-specific SARS-CoV-2 viral diversification to vaccine failure remains unclear. This study analyzed 595 SARS-CoV-2 sequences collected from the Military Health System beneficiaries between December 2020 and April 2022 to investigate the impact of vaccination on viral diversity. By comparing sequences based on the vaccination status of the participant, we found limited evidence indicating that vaccination was associated with increased viral diversity in the SARS-CoV-2 spike, and we show little to no evidence of a substantial sieve effect within major variants; rather, we show that rapid variant replacement constrained intragenotype COVID-19 vaccine strain immune escape. These data suggest that, during past and perhaps future periods of rapid SARS-CoV-2 variant replacement, vaccine-mediated effects were subsumed with other drivers of viral diversity due to the massive scale of infections and vaccinations that occurred in a short time frame. However, our results also highlight some limitations of using sieve analysis methods outside of placebo-controlled clinical trials.

Onward Virus Transmission after Measles Secondary Vaccination Failure.

Measles in persons with secondary vaccination failure (SVF) may be less infectious than cases in unvaccinated persons. Our systematic review aimed to assess transmission risk for measles after SVF. We searched PubMed, Embase, and Web of Science databases from their inception dates. Inclusion criteria were articles describing persons who were exposed to measles-infected persons who had experienced SVF. Across the included 14 studies, >3,030 persons were exposed to measles virus from SVF cases, of whom 180 were susceptible, indicating secondary attack rates of 0%-6.25%. We identified 109 cases of SVF from the studies; 10.09% (n = 11) of case-patients transmitted the virus, resulting in 23 further cases and yielding an effective reproduction number of 0.063 (95% CI 0.0-0.5). These findings suggest a remarkably low attack rate for SVF measles cases, suggesting that, In outbreak situations, public health management of unvaccinated persons could be prioritized over persons with SVF.

Genome sequencing of canine distemper virus isolates from unvaccinated dogs in Mongolia

Canine distemper virus (CDV) triggers a severe, often fatal disease in dogs and wildlife known as canine distemper (CD). Prior research has noted significant genetic diversity and recombination among CDV isolates from different geographical regions, potentially contributing to vaccine failures. Despite this, no genetic characterization of Mongolian CDVs has been conducted. This study, isolated CDVs from three unvaccinated dogs: two 10-month-old mixed-breeds and an 18-month-old Samoyed. All exhibited CD symptoms and subsequently died. Virus isolation was conducted using Vero/dog SLAM cells, with genome sequencing performed via nanopore technology. The mixed-breed dogs were infected with non-recombinant CDV isolates, forming a sister clade to the Asia-1 lineage prevalent in Asia. The Samoyed was infected with a non-recombinant CDV isolate, classifying as Asia-4 lineage sporadically reported in some Asian countries. This sequencing data offers foundational information on genetic diversity, aiding CD control measure development and benefiting future Eurasia and Asian studies.

Whole-genome sequence analysis of canine parvovirus reveals replacement with a novel CPV-2c strain throughout India.

Canine parvovirus (CPV) infection causes severe gastroenteritis in canines, with high mortality in puppies. This virus evolved from feline panleukopenia virus by altering its transferrin receptor (TfR), followed by the emergence of CPV-2 variants in subsequent years with altered immunodominant amino acid residues in the VP2 protein. While previous studies have focused on the VP2 gene, there have been fewer studies on non-structural protein (NS1 and NS2) genes. In the present study, CPV genome sequences from clinical samples collected from canines throughout India in 2023, previous Indian CPV isolates from 2009-2019, and the current Indian CPV vaccine strain were compared. The study showed that the CPV-2c (N426E) variant had almost completely replaced the previously dominant CPV-2a variant (N426) in India. The Q370R mutation of VP2 was the most common change in the recent CPV-2c strain (CPV-2c 370Arg variant). Phylogenetic analysis showed the existence of three clades among the recent CPV-2c strains, and sequence analysis identified several new sites of positive selection in the VP1 (N-terminus), VP2, NS1, and NS2 protein-encoding genes in recent CPV strains, indicating the emergence of new CPV-2c variants with varied antigenic and replication properties. The predominant 'CPV-2c 370Arg variants' were grouped with the Chinese and Nigerian CPV-2c strains but were separate from the CPV vaccine strain and earlier isolates from our repository. VP2 epitope analysis predicted nine amino acid variations (including two new variations) in four potential linear B-cell epitopes in the CPV-2c 370Arg variants that might make vaccine failure more likely. This pan-Indian study lays the foundation for further research concerning the dynamics of virus evolution and understanding genetic mutations.

Comparison of measles plaque reduction neutralization test (PRNT) and measles virus-specific IgG ELISA for assessment of immunogenicity of measles-mumps-rubella vaccination at 5–7 months of age and maternal measles antibodies

BackgroundAssessing the risk of measles outbreaks and identifying the susceptible parts of the population is essential to timely intervention. Infants between 6–12 months are increasingly susceptible to measles but evaluating the performance of high throughput enzyme immunoassays (ELISAs) in infants < 9 months of age is lacking. MethodsA commercially available ELISA kit (Creative Diagnostics, DEIA359) for estimating measles seroprotection was evaluated in infants 5–7 months of age. In an immunogenicity substudy in the Danish MMR trial conducted between 2019–2021, infants (and mothers at baseline) were sampled before and one month after measles-mumps-rubella vaccination (MMR) or placebo as well as one month after routine MMR at 15 months. Measles IgG ELISA was compared to the gold standard but labor-intensive measles plaque reduction neutralization test (PRNT) by Pearson and Spearman correlations and by estimating sensitivity, specificity, and positive and negative predictive values (PPV and NPV). FindingsMeasles IgG levels compared to PRNT antibodies had a Pearson’s correlation coefficient between 0.10–0.24. Seroprotection rates measured by ELISA in young infants were 10–14% lower than measured by PRNT. The sensitivity of the ELISA to detect serological protection compared to PRNT in the infant population differed markedly across sampling time points and was 14%, 40%, and 92% at baseline, post-intervention, and post-routine MMR, whereas the specificity was 99%, 93%, and 43%, respectively. The PPV and NPV were 68% and 87% in infants at baseline. InterpretationThe correlation between measles IgG and PRNT antibodies was low. Seroprotection was underestimated using ELISA. High-accuracy tests are needed to avoid misclassifications and practices that lead to primary or secondary vaccine failure or retention of vaccination in outbreak settings. Baseline PPV and NPV suggested some applicability of ELISA in predicting serological protection in this age group. However, PRNT may be the only accurate estimator of serological protection in young infants.

Unlocking the puzzle: non-defining mutations in SARS-CoV-2 proteome may affect vaccine effectiveness.

SARS-CoV-2 variants are defined by specific genome-wide mutations compared to the Wuhan genome. However, non-clade-defining mutations may also impact protein structure and function, potentially leading to reduced vaccine effectiveness. Our objective is to identify mutations across the entire viral genome rather than focus on individual mutations that may be associated with vaccine failure and to examine the physicochemical properties of the resulting amino acid changes. Whole-genome consensus sequences of SARS-CoV-2 from COVID-19 patients were retrieved from the GISAID database. Analysis focused on Dataset_1 (7,154 genomes from Italy) and Dataset_2 (8,819 sequences from Spain). Bioinformatic tools identified amino acid changes resulting from codon mutations with frequencies of 10% or higher, and sequences were organized into sets based on identical amino acid combinations. Non-defining mutations in SARS-CoV-2 genomes belonging to clades 21 L (Omicron), 22B/22E (Omicron), 22F/23A (Omicron) and 21J (Delta) were associated with vaccine failure. Four sets of sequences from Dataset_1 were significantly linked to low vaccine coverage: one from clade 21L with mutations L3201F (ORF1a), A27- (S) and G30- (N); two sets shared by clades 22B and 22E with changes A27- (S), I68- (S), R346T (S) and G30- (N); and one set shared by clades 22F and 23A containing changes A27- (S), F486P (S) and G30- (N). Booster doses showed a slight improvement in protection against Omicron clades. Regarding 21J (Delta) two sets of sequences from Dataset_2 exhibited the combination of non-clade mutations P2046L (ORF1a), P2287S (ORF1a), L829I (ORF1b), T95I (S), Y145H (S), R158- (S) and Q9L (N), that was associated with vaccine failure. Vaccine coverage associations appear to be influenced by the mutations harbored by marketed vaccines. An analysis of the physicochemical properties of amino acid revealed that primarily hydrophobic and polar amino acid substitutions occurred. Our results suggest that non-defining mutations across the proteome of SARS-CoV-2 variants could affect the extent of protection of the COVID-19 vaccine. In addition, alteration of the physicochemical characteristics of viral amino acids could potentially disrupt protein structure or function or both.