Seroprevalence of coxsackievirus A21 neutralizing antibodies in Yamagata, Japan between 1976 and 2019; coxsackievirus A21 has rarely affected young children

2021 ◽  
Author(s):  
Waka Tanaka ◽  
Kenichi Komabayashi ◽  
Yoko Ikeda ◽  
Yoko Aoki ◽  
Tsutomu Itagaki ◽  
...  
Keyword(s):  
Young Children ◽  
Neutralizing Antibodies ◽  
Coxsackievirus A21

scholarly journals Development of intravenously administered synthetic RNA virus immunotherapy for the treatment of cancer

2021 ◽  
Author(s):  
Edward Kennedy ◽  
Agnieszka Denslow ◽  
Jacqueline Hewett ◽  
Lingxin Kong ◽  
Ana De Almeida ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Immune Cell ◽  
Rna Virus ◽  
Neutralizing Antibody ◽  
Repeated Administration ◽  
Oncolytic Viruses ◽  
Drug Candidates ◽  
Novel Approach ◽  
Coxsackievirus A21 ◽  
Anti Tumor Activity

Abstract Oncolytic viruses (OVs) are an emerging therapeutic approach for the treatment of cancer. Clinical benefit has been demonstrated for intratumoral administration, but the therapeutic effectiveness of intravenous delivery has been limited by neutralizing antibody responses against the virus. To circumvent this limitation, we developed Synthetic RNA viruses, a novel approach for intravenous and repeated administration of OVs, consisting of a viral RNA genome (vRNA) formulated within lipid nanoparticles. For two Synthetic RNA virus drug candidates, Seneca Valley virus (SVV) and Coxsackievirus A21 (CVA21), we demonstrate vRNA delivery, viral replication, spread, and lysis of tumor cells leading to potent anti-tumor efficacy, even in the presence of OV neutralizing antibodies in the bloodstream. Synthetic-SVV replication in tumors promoted immune cell infiltration and enhanced anti-tumor activity in combination with anti-PD-1 checkpoint inhibitor. Altogether, the Synthetic RNA virus platform provides an innovative approach that enables repeat intravenous administration of viral immunotherapy.

scholarly journals 846. Postnatally Acquired Zika Virus (ZIKV) Infection in Infants and Young Children in Guatemala: Serologic and Neurodevelopmental (ND) Evaluation

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S14-S15
Author(s):  
Flor M Munoz ◽  
Flor M Munoz ◽  
Amy Connery ◽  
Muktha S Natrajan ◽  
Jesse Waggoner ◽  
...  
Keyword(s):  
Young Children ◽  
Early Life ◽  
Neutralizing Antibodies ◽  
Denv Infection ◽  
Population Based ◽  
Cross Reactivity ◽  
Zikv Infection ◽  
Material Support ◽  
Serologic Evidence ◽  
Research Grant

Abstract Background Diagnosing ZIKV infection in children in dengue (DENV) endemic regions is challenging. The kinetics and effects of maternal Ab on infant infection responses remain unknown, as do the ND effects of ZIKV acquired in early life. Methods This is a population-based prospective cohort study in infant–mother pairs and children <5 years in a rural DENV endemic area of Guatemala evaluating the incidence and ND outcomes of postnatally cquired ZIKV infection. Subjects were followed 1 year for symptoms of flavivirus-like illness (FLI), serologic and virologic evidence of ZIKV or DENV infection and ND outcomes. ZIKV and DENV neutralizing antibodies (NAb) were measured at enrollment and longitudinally. Subjects were classified as ZIKV- or DENV-infected based on NAb. Specimens from acute illnesses were tested for viral RNA by rRT-PCR. ND was assessed at enrollment and longitudinally using an adapted Mullen Scales of Early Learning (MSEL). Results In total, 1,371 subjects (374 children 1–5 years, 500 infants, 497 mothers) were enrolled from June 2017 to July 2018. Among 1,335 evaluable subjects, 7.6% (101) had serologic evidence of recent ZIKV infection (NAb >500 or >100 and DENV-neg); 13.2% (176) were DENV-pos only; 44.8% (598) were ZIKV-neg (NAb15 −<100) or low (<500) ZIKV and DENV NAb, suggesting prior flavivirus infection or cross-reactivity (Figures 1 and 2). ZIKV infection alone was more prevalent in children 1–5 years, while infants’ serologic pattern was similar to that of their mothers. One child ZIKV seroconverted. In 391 FLI episodes (67 children 1–5 years and 215 infants with fever, rash, myalgia, and conjunctivitis; 109 mothers with fever, myalgia, and joint pain), acute DENV infections, but not ZIKV, were identified by rRT-PCR. MSEL scores were similar to US norms in infants <12 m (composite mean 94.8, SD 11.9), but lower in children 1–5 years in all domains (mean 75.1, SD 17.4, P < 0.0001) (Figure 3). Conclusion Serologic evidence of recent ZIKV infection, but no acute ZIKV, was documented in young children in Guatemala. Infant seroreactivity derives from prior maternal infection and DENV cross-reactivity. Observed substantial differences in ND scores between infants and children 1–5 years challenge the ability to isolate the potential effects of ZIKV infection in early life. NIAID Contract HHSN272201300015I Task Order HHSN27200013. FMM and EJA Co-PIs. Disclosures Flor M. Munoz, MD, Biocryst: Grant/Research Support; CDC: Research Grant; Moderna: Other Financial or Material Support, Safety Monitoring Board Member/Chair; NIH: Research Grant; Novavax: Research Grant; UP to Date: Author and Editor: Royalties, Other Financial or Material Support.

scholarly journals Alternative Virus-Like Particle-Associated Prefusion F Proteins as Maternal Vaccines for Respiratory Syncytial Virus

2019 ◽  
Vol 93 (23) ◽  
Author(s):  
Jorge C. G. Blanco ◽  
Lurds R. Fernando ◽  
Wei Zhang ◽  
Arash Kamali ◽  
Marina S. Boukhvalova ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Young Children ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
F Protein ◽  
Maternal Immunization ◽  
Maternal Vaccination ◽  
Virus Like Particle ◽  
Cotton Rats ◽  
Syncytial Virus

ABSTRACT Maternal vaccination may be the most effective and safest approach to the protection of infants from respiratory syncytial virus (RSV) infection, a severe acute lower respiratory tract disease in infants and young children worldwide. We previously compared five different virus-like particle (VLP)-associated, mutation-stabilized prefusion F (pre-F) proteins, including the prototype DS-Cav1 F VLPs. We showed that alternative versions of prefusion F proteins have different conformations and induce different populations of anti-F protein antibodies. Two of these alternative pre-F VLPs, the UC-2 F and UC-3 F VLPs, stimulated in mice higher titers of neutralizing antibodies than DS-Cav1 F VLPs (M. L. Cullen, R. M. Schmidt, M. G. Torres, A. A. Capoferri, et al., Vaccines 7:21–41, 2019, https://doi.org/10.3390/vaccines7010021). Here we describe a comparison of these two pre-F VLPs with DS-Cav1 F VLPs as maternal vaccines in cotton rats and report that UC-3 F VLPs significantly increased the neutralizing antibody (NAb) titers in pregnant dams compared to DS-Cav1 F VLPs. The neutralizing antibody titers in the sera of the offspring of the dams immunized with UC-3 F VLPs were significantly higher than those in the sera of the offspring of dams immunized with DS-Cav1 VLPs. This increase in serum NAb titers translated to a 6- to 40-fold lower virus titer in the lungs of the RSV-challenged offspring of dams immunized with UC-3 F VLPs than in the lungs of the RSV-challenged offspring of dams immunized with DS-Cav1 F VLPs. Importantly, the offspring of UC-3 F VLP-immunized dams showed significant protection from lung pathology and from induction of inflammatory lung cytokine mRNA expression after RSV challenge. Immunization with UC-3 F VLPs also induced durable levels of high-titer neutralizing antibodies in dams. IMPORTANCE Respiratory syncytial virus (RSV) is a significant human pathogen severely impacting neonates and young children, but no vaccine exists to protect this vulnerable population. Furthermore, direct vaccination of neonates is likely ineffective due to the immaturity of their immune system, and neonate immunization is potentially unsafe. Maternal vaccination may be the best and safest approach to the protection of neonates through the passive transfer of maternal neutralizing antibodies in utero to the fetus after maternal immunization. Here we report that immunization of pregnant cotton rats, a surrogate model for human maternal immunization, with novel RSV virus-like particle (VLP) vaccine candidates containing stabilized prefusion RSV F proteins provides significant levels of protection of the offspring of immunized dams from RSV challenge. We also found that antibodies induced by VLPs containing different versions of the prefusion F protein varied by 40-fold in the extent of protection provided to the offspring of vaccinated dams upon RSV challenge.

scholarly journals Prevalence of IgG and Neutralizing Antibodies againstStaphylococcus aureusAlpha-Toxin in Healthy Human Subjects and Diverse Patient Populations

2017 ◽  
Vol 86 (3) ◽  
Author(s):  
Yuling Wu ◽  
Xu Liu ◽  
Ahmad Akhgar ◽  
Jia J. Li ◽  
Hoyin Mok ◽  
...  
Keyword(s):  
Young Children ◽  
Neutralizing Antibodies ◽  
Human Subjects ◽  
Age Groups ◽  
Surgical Site Infections ◽  
Neutralizing Antibody ◽  
High Morbidity ◽  
Healthy Human ◽  
Content Type ◽  
Antibody Levels

ABSTRACTStaphylococcus aureuscauses an array of serious infections resulting in high morbidity and mortality worldwide. This study evaluated naturally occurring serum anti-alpha-toxin (anti-AT) antibody levels in human subjects from various age groups, individuals withS. aureusdialysis and surgical-site infections, andS. aureus-colonized versus noncolonized subjects. Anti-AT immunoglobulin G (IgG) and neutralizing antibody (NAb) levels in infants (aged ≤1 year) were significantly lower than those in other populations. In comparison to adolescent, adult, and elderly populations, young children (aged 2 to 10 years) had equivalent anti-AT IgG levels but significantly lower anti-AT NAb levels. Therefore, the development of anti-AT NAbs appears to occur later than that of AT-specific IgG, suggesting a maturation of the immune response to AT. Anti-AT IgG levels were slightly higher inS. aureus-colonized subjects than in noncolonized subjects. The methicillin susceptibility status of colonizing isolates had no effect on anti-AT antibody levels inS. aureus-colonized subjects. The highest anti-AT IgG and NAb levels were observed in dialysis patients with acuteS. aureusinfection. Anti-AT IgG and NAb levels were well correlated in subjects aged >10 years, regardless of colonization or infection status. These data demonstrate that AT elicits a robust IgG humoral response in infants and young children that becomes stable prior to adolescence, matures into higher levels of NAbs in healthy adolescents, and becomes elevated duringS. aureusinfection. These findings may assist in identifying subjects and patient populations that could benefit from vaccination or immunoprophylaxis with anti-AT monoclonal antibodies.

scholarly journals Evaluation of Clinical and Immune Responses in Recovered Children with Mild COVID-19

Viruses ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 85
Author(s):  
Xiaodong Tian ◽  
Zhihua Bai ◽  
Ying Cao ◽  
Haizhou Liu ◽  
Di Liu ◽  
...  
Keyword(s):  
Young Children ◽  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Immune Memory ◽  
Lung Lesions ◽  
Significant Difference ◽  
Specific Igg ◽  
Cellular Immune ◽  
Infants And Young Children

The coronavirus disease 2019 (COVID-19) has spread globally and variants continue to emerge, with children are accounting for a growing share of COVID-19 cases. However, the establishment of immune memory and the long-term health consequences in asymptomatic or mildly symptomatic children after severe acute respiratory syndrome coronavirus 2 infection are not fully understood. We collected clinical data and whole blood samples from discharged children for 6–8 months after symptom onset among 0-to-14-year-old children. Representative inflammation signs returned to normal in all age ranges. The infants and young children (0–4 years old) had lung lesions that persisted for 6–8 months and were less responsive for antigen-specific IgG secretion. In the 5-to-14-year-old group, lung imaging abnormalities gradually recovered, and the IgG-specific antibody response was strongest. In addition, we found a robust IgM+ memory B cell response in all age. Memory T cells specific for the spike or nucleocapsid protein were generated, with no significant difference in IFN-γ response among all ages. Our study highlights that although lung lesions caused by COVID-19 can last for at least 6–8 months in infants and young children, most children have detectable residual neutralizing antibodies and specific cellular immune responses at this stage.

Rapid Disappearance of Poliovirus Type 2 (PV2) Immunity in Young Children Following Withdrawal of Oral PV2-Containing Vaccine in Vietnam

2019 ◽  
Vol 220 (3) ◽  
pp. 386-391 ◽  
Author(s):  
Dang Thi Thanh Huyen ◽  
Ondrej Mach ◽  
Nguyen Thanh Trung ◽  
Pham Quang Thai ◽  
Ho Vinh Thang ◽  
...  
Keyword(s):  
Young Children ◽  
Blood Sample ◽  
Neutralizing Antibodies ◽  
Oral Vaccine ◽  
Age Groups ◽  
Cross Sectional Survey ◽  
Cross Sectional ◽  
Poliovirus Type ◽  
Population Immunity

Abstract Background Due to global shortage of inactivated poliovirus vaccine and withdrawal of oral vaccine containing poliovirus type 2 (PV2), a PV2-containing vaccine was not used in Vietnam May 2016 to October 2018. We assessed the population immunity gap to PV2. Methods A cross-sectional survey in children aged 1–18 months was carried out in January 2018. One blood sample per child was analyzed for presence of poliovirus neutralizing antibodies. In children with detectable anti-PV2 antibodies, a second sample was analyzed 4 months later to distinguish between passive (maternally derived) and active (induced by secondary transmission or vaccination) immunity. Results Sera were obtained from 1106/1110 children. Seroprevalence of PV2 antibodies was 87/368 (23.6%) at age 1–7 months, 27/471 (5.7%) at 8–15 months, and 19/267 (7.1%) at 16–18 months. Seroprevalence declined with age in the 1–7 months group; in the 8–18 months group there was no significant change with age. Four months later, 11/87 (14%), 9/27 (32%), and 12/19 (37%) remained seropositive in 1–7, 8–15, and 16–18 months age groups, respectively. Conclusions We found declining immunity to PV2, suggesting Vietnam is at risk for an outbreak of type 2 vaccine-derived poliovirus following virus importation or new emergence.

The Modification of Hypernasality in Young Children

1984 ◽  
Vol 15 (1) ◽  
pp. 37-43 ◽  
Author(s):  
Moya L. Andrews ◽  
Sarah J. Tardy ◽  
Lisa G. Pasternak
Keyword(s):  
Young Children ◽  
Voice Therapy

This paper presents an approach to voice therapy programming for young children who are hypernasal. Some general principles underlying the approach are presented and discussed.

Lexical Comprehension in Young Children With Developmental Delays

1994 ◽  
Vol 3 (1) ◽  
pp. 79-88 ◽  
Author(s):  
Theresa A. Kouri
Keyword(s):  
Young Children ◽  
Developmental Delays ◽  
Normal Development ◽  
Clinical Applications ◽  
Group Status ◽  
Novel Object ◽  
Related Information ◽  
Comprehension Skills ◽  
Lexical Items ◽  
Lexical Concepts

Lexical comprehension skills were examined in 20 young children (aged 28–45 months) with developmental delays (DD) and 20 children (aged 19–34 months) with normal development (ND). Each was assigned to either a story-like script condition or a simple ostensive labeling condition in which the names of three novel object and action items were presented over two experimental sessions. During the experimental sessions, receptive knowledge of the lexical items was assessed through a series of target and generalization probes. Results indicated that all children, irrespective of group status, acquired more lexical concepts in the ostensive labeling condition than in the story narrative condition. Overall, both groups acquired more object than action words, although subjects with ND comprehended more action words than subjects with DD. More target than generalization items were also comprehended by both groups. It is concluded that young children’s comprehension of new lexical concepts is facilitated more by a context in which simple ostensive labels accompany the presentation of specific objects and actions than one in which objects and actions are surrounded by thematic and event-related information. Various clinical applications focusing on the lexical training of young children with DD are discussed.

Eliciting Verbs From Children With Specific Language Impairment

1996 ◽  
Vol 5 (4) ◽  
pp. 17-30 ◽  
Author(s):  
Diane Frome Loeb ◽  
Clifton Pye ◽  
Sean Redmond ◽  
Lori Zobel Richardson
Keyword(s):  
Young Children ◽  
Language Impairment ◽  
Specific Language Impairment ◽  
Syntactic Complexity ◽  
Specific Language ◽  
Lexical Skills

The focus of assessment and intervention is often aimed at increasing the lexical skills of young children with language impairment. Frequently, the use of nouns is the center of the lexical assessment. As a result, the production of verbs is not fully evaluated or integrated into treatment in a way that accounts for their semantic and syntactic complexity. This paper presents a probe for eliciting verbs from children, describes its effectiveness, and discusses the utility of and problems associated with developing such a probe.

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