Transplacental Respiratory Syncytial Virus and Influenza Virus Antibody Transfer in Alaska Native and Seattle Mother–Infant Pairs

Abstract Background Alaska Native (AN) infants are at risk for severe disease due to respiratory syncytial virus (RSV) and influenza. Maternal immunization protects young infants through transplacental antibody transfer. RSV- and influenza-specific transplacental antibody transfer in mother–infant pairs has not previously been evaluated in the AN population. Methods Serum samples collected during pregnancy and at birth from AN mother–infant pairs in the Yukon-Kuskokwim Delta region (YKD) of Alaska (2000–2011; n = 75) and predominantly white pairs in Seattle, Washington (2014–2016; n = 57), were tested for RSV and influenza antibody using a microneutralization and hemagglutination inhibition assay, respectively, and compared between sites. Results Mean RSV antibody concentrations in pregnant women in YKD and Seattle were similar (log2 RSV antibody 10.6 vs 10.7, P = .86), but cord blood RSV antibody concentrations were significantly lower in infants born to mothers in YKD compared with Seattle (log2 RSV antibody 11.0 vs 12.2, P < .001). Maternal and cord blood influenza antibody concentrations were lower for women and infants in YKD compared with Seattle for all 4 influenza antigens tested (all P < .05). The mean cord to maternal RSV antibody transfer ratio was 1.15 (standard deviation [SD], 0.13) in mother–infant pairs in Seattle compared with 1.04 (SD, 0.08) in YKD. Mean cord blood to maternal antibody transfer ratios for influenza antigens ranged from 1.22 to 1.42 in Seattle and from 1.05 to 1.59 in YKD. Conclusions Though the transplacental antibody transfer ratio was high (>1.0) for both groups, transfer ratios for RSV antibody were significantly lower in AN mother–infant pairs. Further studies are needed to elucidate the impact of lower transplacental antibody transfer on infant disease risk in rural Alaska. Alaska Native and continental US mother-infant pairs have high transplacental antibody transfer ratios (>1.0) for influenza and respiratory syncytial virus, but anti-respiratory syncytial virus antibody levels are significantly lower in Alaska Native pairs than in those from the continental US.

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Respiratory Syncytial Virus (RSV) Neutralizing Antibodies at Birth Predict Protection from RSV Illness in Infants in the First 3 Months of Life

Clinical Infectious Diseases ◽

10.1093/cid/ciaa648 ◽

2020 ◽

Cited By ~ 4

Author(s):

Andrea G Buchwald ◽

Barney S Graham ◽

Awa Traore ◽

Fadima Cheick Haidara ◽

Man Chen ◽

...

Keyword(s):

Respiratory Syncytial Virus ◽

Cord Blood ◽

Neutralizing Antibodies ◽

Maternal Immunization ◽

Young Infants ◽

Healthy Control ◽

Antibody Titers ◽

Syncytial Virus ◽

Antibody Levels ◽

Nested Case Control

Abstract Background Respiratory syncytial virus (RSV) is a leading cause of viral pneumonia and bronchiolitis during the first 6 months of life. Placentally transferred antibodies can prevent severe RSV illness, and maternal immunization may reduce illness in young infants. Identification of protective antibody levels facilitates the advancement of vaccine candidates and maternal immunization. Methods We conducted a nested case-control study with 587 Malian mother–infant pairs, followed from birth to age 6 months. RSV cases were infants who developed influenza-like illness (ILI) or pneumonia and were RSV-positive by polymerase chain reaction. Cases were matched to healthy controls and RSV-negative ILI controls. RSV-A and RSV-B neutralizing antibodies were measured in maternal, cord blood, and infant sera at age 3 and 6 months. Results Maternal antibodies were efficiently transferred to infants. Maternal and infant RSV titers were strongly correlated. Infant antibody titers against RSV-A were 3 times higher than those against RSV-B. At birth, infants who remained healthy had significantly higher RSV-A and RSV-B titers compared with infants who subsequently contracted RSV. RSV-A inhibitory concentration (IC)80 titer >239 or RSV-B titer >60 at birth was significantly associated with being a healthy control compared with an RSV case within the first 3 months of life. RSV-A IC80 titers in cord blood were associated with decreased episodes of pneumonia. Conclusions Maternally acquired RSV antibodies were associated with protection of infants against community-detected cases of RSV-ILI and pneumonia. RSV titers in cord blood can predict whether an infant will be infected with RSV or remain uninfected.

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Lack of Activation Marker Induction and Chemokine Receptor Switch in Human Neonatal Myeloid Dendritic Cells in Response to Human Respiratory Syncytial Virus

Journal of Virology ◽

10.1128/jvi.01216-19 ◽

2019 ◽

Vol 93 (22) ◽

Cited By ~ 2

Author(s):

Cyril Le Nouën ◽

Philippa Hillyer ◽

Eric Levenson ◽

Craig Martens ◽

Ronald L. Rabin ◽

...

Keyword(s):

Immune Response ◽

Dendritic Cells ◽

Respiratory Syncytial Virus ◽

Immune Responses ◽

Cord Blood ◽

Influenza A ◽

Adaptive Immune Response ◽

Adaptive Immune ◽

Young Infants ◽

Syncytial Virus

ABSTRACT Respiratory syncytial virus (RSV) infects and causes disease in infants and reinfects with reduced disease throughout life without significant antigenic change. In contrast, reinfection by influenza A virus (IAV) largely requires antigenic change. The adaptive immune response depends on antigen presentation by dendritic cells (DC), which may be too immature in young infants to induce a fully protective immune response against RSV reinfections. We therefore compared the ability of RSV and IAV to activate primary human cord blood (CB) and adult blood (AB) myeloid DC (mDC). While RSV and IAV infected with similar efficiencies, RSV poorly induced maturation and cytokine production in CB and AB mDC. This difference between RSV and IAV was more profound in CB mDC. While IAV activated CB mDC to some extent, RSV did not induce CB mDC to increase the maturation markers CD38 and CD86 or CCR7, which directs DC migration to lymphatic tissue. Low CCR7 surface expression was associated with high expression of CCR5, which keeps DC in inflamed peripheral tissues. To evaluate a possible inhibition by RSV, we subjected RSV-inoculated AB mDC to secondary IAV inoculation. While RSV-inoculated AB mDC responded to secondary IAV inoculation by efficiently upregulating activation markers and cytokine production, IAV-induced CCR5 downregulation was slightly inhibited in cells exhibiting robust RSV infection. Thus, suboptimal stimulation and weak and mostly reversible inhibition seem to be responsible for inefficient mDC activation by RSV. The inefficient mDC stimulation and immunological immaturity in young infants may contribute to reduced immune responses and incomplete protection against RSV reinfection. IMPORTANCE Respiratory syncytial virus (RSV) causes disease early in life and can reinfect symptomatically throughout life without undergoing significant antigenic change. In contrast, reinfection by influenza A virus (IAV) requires antigenic change. The adaptive immune response depends on antigen presentation by dendritic cells (DC). We used myeloid DC (mDC) from cord blood and adult blood donors to evaluate whether immunological immaturity contributes to the inability to mount a fully protective immune response to RSV. While IAV induced some activation and chemokine receptor switching in cord blood mDC, RSV did not. This appeared to be due to a lack of activation and a weak and mostly reversible inhibition of DC functions. Both viruses induced a stronger activation of mDC from adults than mDC from cord blood. Thus, inefficient stimulation of mDC by RSV and immunological immaturity may contribute to reduced immune responses and increased susceptibility to RSV disease and reinfection in young infants.

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Temporal Dysbiosis of Infant Nasal Microbiota Relative to Respiratory Syncytial Virus Infection

10.1101/2020.04.30.071258 ◽

2020 ◽

Cited By ~ 1

Author(s):

Alex Grier ◽

Ann L. Gill ◽

Haeja A. Kessler ◽

Anthony Corbett ◽

Sanjukta Bandyopadhyay ◽

...

Keyword(s):

Respiratory Syncytial Virus ◽

Respiratory Disease ◽

Disease Severity ◽

Disease Risk ◽

Developmental Trajectory ◽

Microbiota Composition ◽

Rsv Infection ◽

Syncytial Virus ◽

The Impact ◽

Nasal Microbiota

ABSTRACTRationaleRespiratory Syncytial Virus (RSV) infection is a leading cause of infant respiratory disease and hospitalization. Infant airway microbiota occupying the nasopharynx have been associated with respiratory disease risk and severity. The extent to which interactions between RSV and microbiota occur in the airway, and their impact on respiratory disease severity and infection susceptibility, are not well understood.ObjectivesTo characterize associations between the nasal microbiota and RSV infection before, during, and after infants’ first respiratory illness.MethodsNasal 16S rRNA microbial community profiling of two cohorts of infants in the first year of life: 1) a cross-sectional cohort of 89 RSV infected infants sampled during illness and 102 population matched healthy controls, and 2) an individually matched longitudinal cohort of 12 infants who developed RSV infection and 12 who did not, sampled at time points before, during, and after infection.Measurements and Main ResultsWe identified 12 taxa significantly associated with RSV infection. All 12 were differentially abundant during infection, with seven differentially abundant prior to infection, and eight differentially abundant after infection. Eight of these taxa were associated with disease severity. Nasal microbiota composition was more discriminative of healthy vs. infected than of disease severity.ConclusionsOur findings elucidate the chronology of nasal microbiota dysbiosis and suggest an altered developmental trajectory associated with first-time RSV infection. Microbial temporal dynamics reveal indicators of disease risk, correlates of illness and severity, and the impact of RSV infection on microbiota composition. Identified taxa represent appealing targets for additional translationally-oriented research.

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Transmission of Respiratory Syncytial Virus Among Children Under 5 Years in Households of Rural Communities, the Philippines

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz045 ◽

2019 ◽

Vol 6 (3) ◽

Author(s):

Hirono Otomaru ◽

Taro Kamigaki ◽

Raita Tamaki ◽

Michiko Okamoto ◽

Portia Parian Alday ◽

...

Keyword(s):

Respiratory Syncytial Virus ◽

Single Case ◽

The Philippines ◽

Older Children ◽

Primary Case ◽

Young Infants ◽

Serial Interval ◽

Rsv Infection ◽

Syncytial Virus ◽

The Impact

Abstract Background To develop a more effective vaccination strategy for reducing the impact of respiratory syncytial virus (RSV) infection, especially in young infants (<6 months old), it is necessary to understand the transmission dynamics of RSV. Methods We conducted a community-based prospective cohort study from 2014 to 2016 in Biliran Province, the Philippines, on children <5 years old. We collected nasopharyngeal swabs from symptomatic children with acute respiratory infection (ARI) during household visits and at health facilities. In households (n = 181) with RSV-positive ARI cases (RSV-ARI), we also identified ARI episodes among other children <5 years old in the same household. In addition, we determined the serial interval to estimate the basic reproduction number (R0), the average number of secondary cases generated by a single primary case. Results In the 181 households analyzed, we found 212 RSV-ARI in 152 households with a single case and 29 households with multiple cases, which included 29 1st RSV-ARI and 31 2nd RSV-ARI. We also found possible index cases among children <5 years old in the same household for 29.0% (18 of 62) of young infants with RSV-ARI. The estimated mean serial interval was 3.2 days, and R0 was estimated to be 0.92–1.33 for RSV-A and 1.04–1.76 for RSV-B, which varied between different times (2014 and 2015) and places. Conclusions Young infants are likely to acquire RSV infection from older children in the same household. Therefore, vaccination targeting older children might protect infants from RSV infection.

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Human Respiratory Syncytial Virus Subgroup A and B Infections in Nasal, Bronchial, Small-Airway, and Organoid-Derived Respiratory Cultures

mSphere ◽

10.1128/msphere.00237-21 ◽

2021 ◽

Vol 6 (3) ◽

Author(s):

L. C. Rijsbergen ◽

M. M. Lamers ◽

A. D. Comvalius ◽

R. W. Koutstaal ◽

D. Schipper ◽

...

Keyword(s):

Cell Culture ◽

Respiratory Syncytial Virus ◽

Severe Disease ◽

Small Airway ◽

Human Respiratory Syncytial Virus ◽

Model Systems ◽

Young Infants ◽

Culture Models ◽

Syncytial Virus ◽

Cell Culture Models

ABSTRACT Human respiratory syncytial virus (HRSV) is the leading cause of bronchiolitis in infants. Two subgroups of HRSV (A and B) routinely cocirculate. Most research has been performed with HRSV-A strains because these are easier to culture than HRSV-B strains. In this study, we aimed to compare the replicative fitness and HRSV-induced innate cytokine responses of HRSV-A and HRSV-B strains in disease-relevant cell culture models. We used two recombinant (r) clinical isolate-based HRSV strains (A11 and B05) and one recombinant laboratory-adapted HRSV strain (A2) to infect commercially available nasal, bronchial, and small-airway cultures. Epithelial cells from all anatomical locations were susceptible to HRSV infection despite the induction of a dominant type III interferon response. Subgroup A viruses disseminated and replicated faster than the subgroup B virus. Additionally, we studied HRSV infection and innate responses in airway organoids (AOs) cultured at air-liquid interface (ALI). Results were similar to the commercially obtained bronchial cells. In summary, we show that HRSV replicates well in cells from both the upper and the lower airways, with a slight replicative advantage for subgroup A viruses. Lastly, we showed that AOs cultured at ALI are a valuable model for studying HRSV ex vivo and that they can be used in the future to study factors that influence HRSV disease severity. IMPORTANCE Human respiratory syncytial virus (HRSV) is the major cause of bronchiolitis and pneumonia in young infants and causes almost 200,000 deaths per year. Currently, there is no vaccine or treatment available, only a prophylactic monoclonal antibody (palivizumab). An important question in HRSV pathogenesis research is why only a fraction (1 to 3%) of infants develop severe disease. Model systems comprising disease-relevant HRSV isolates and accurate and reproducible cell culture models are indispensable to study infection, replication, and innate immune responses. Here, we used differentiated AOs cultured at ALI to model the human airways. Subgroup A viruses replicated better than subgroup B viruses, which we speculate fits with epidemiological findings that subgroup A viruses cause more severe disease in infants. By using AOs cultured at ALI, we present a highly relevant, robust, and reproducible model that allows for future studies into what drives severe HRSV disease.

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Respiratory syncytial virus in severe lower respiratory infections in previously healthy young Ethiopian infants

BMC Pediatrics ◽

10.1186/s12887-021-02675-3 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Abate Yeshidinber Weldetsadik ◽

Frank Riedel

Keyword(s):

Respiratory Syncytial Virus ◽

Rainy Season ◽

Clinical Laboratory ◽

Respiratory Infections ◽

Clinical Parameter ◽

Imaging Data ◽

Chi Square ◽

Young Infants ◽

Rsv Infection ◽

Syncytial Virus

Abstract Background Respiratory Syncytial Virus (RSV) is the commonest cause of acute lower respiratory infections (ALRI) in infants. However, the burden of RSV is unknown in Ethiopia. We aimed to determine the prevalence, seasonality and predictors of RSV infection in young infants with ALRI for the first time in Ethiopia. Methods We performed RSV immuno-chromatographic assay from nasopharyngeal swabs of infants, 29 days to 6 months of age. We included the first 10 eligible infants in each month from June 2018 to May 2019 admitted in a tertiary pediatric center. Clinical, laboratory and imaging data were also collected, and chi-square test and regression were used to assess associated factors with RSV infection. Results Among a total of 117 study children, 65% were male and mean age was 3 months. Bronchiolitis was the commonest diagnosis (49%). RSV was isolated from 26 subjects (22.2%) of all ALRI, 37% of bronchiolitis and 11% of pneumonia patients. Although RSV infection occurred year round, highest rate extended from June to November. No clinical or laboratory parameter predicted RSV infection and only rainy season (Adjusted Odds Ratio (AOR) 10.46 [95%. C.I. 1.95, 56.18]) was independent predictor of RSV infection. Conclusions RSV was isolated in a fifth of young infants with severe ALRI, mostly in the rainy season. Diagnosis of RSV infection in our setting require specific tests as no clinical parameter predicted RSV infection. Since RSV caused less than a quarter of ALRI in our setting, the other causes should be looked for in future studies.

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1719. Respiratory Syncytial Virus-Associated Hospitalization Rates among US Infants: A Systematic Review and Meta-Analysis

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1897 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S843-S843

Author(s):

John M McLaughlin ◽

Farid L Khan ◽

Heinz-Josef Schmitt ◽

Yasmeen Agosti ◽

Luis Jodar ◽

...

Keyword(s):

Public Health ◽

Respiratory Syncytial Virus ◽

Active Surveillance ◽

Meta Analysis ◽

The United States ◽

Administrative Claims ◽

Prevention Strategies ◽

Hospitalization Rates ◽

Syncytial Virus ◽

The Impact

Abstract Background Understanding the true magnitude of infant respiratory syncytial virus (RSV) burden is critical for determining the potential public-health benefit of RSV prevention strategies. Although global reviews of infant RSV burden exist, none have summarized data from the United States or evaluated how RSV burden estimates are influenced by variations in study design. Methods We performed a systematic literature review and meta-analysis of studies describing RSV-associated hospitalization rates among US infants. We also examined the impact of key study characteristics on these estimates. Results After review of 3058 articles through January 2020, we identified 25 studies with 31 unique estimates of RSV-associated hospitalization rates. Among US infants < 1 year of age, annual rates ranged from 8.4 to 40.8 per 1000 with a pooled rate= 19.4 (95%CI= 17.9–20.9). Study type was associated with RSV hospitalization rates (P =.003), with active surveillance studies having pooled rates per 1000 (11.1; 95%CI: 9.8–12.3) that were half that of studies based on administrative claims (21.4; 95%CI: 19.5–23.3) or modeling approaches (23.2; 95%CI: 20.2–26.2). Conclusion Applying the pooled rates identified in our review to the 2020 US birth cohort suggests that 73,680 to 86,020 RSV-associated infant hospitalizations occur each year. To date, public-health officials have used conservative estimates from active surveillance as the basis for defining US infant RSV burden. The full range of RSV-associated hospitalization rates identified in our review better characterizes the true RSV burden in infants and can better inform future evaluations of RSV prevention strategies. Disclosures John M. McLaughlin, PhD, Pfizer (Employee, Shareholder) Farid L. Khan, MPH, Pfizer (Employee, Shareholder) Heinz-Josef Schmitt, MD, Pfizer (Employee, Shareholder) Yasmeen Agosti, MD, Pfizer (Employee, Shareholder) Luis Jodar, PhD, Pfizer (Employee, Shareholder) Eric Simões, MD, Pfizer (Consultant, Research Grant or Support) David L. Swerdlow, MD, Pfizer (Employee, Shareholder)

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Glycan variants of a respiratory syncytial virus antibody with enhanced effector function and in vivo efficacy

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1402458111 ◽

2014 ◽

Vol 111 (16) ◽

pp. 5992-5997 ◽

Cited By ~ 66

Author(s):

A. Hiatt ◽

N. Bohorova ◽

O. Bohorov ◽

C. Goodman ◽

D. Kim ◽

...

Keyword(s):

Respiratory Syncytial Virus ◽

Effector Function ◽

Virus Antibody ◽

In Vivo Efficacy ◽

Syncytial Virus

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Determining the Seasonality of Respiratory Syncytial Virus in the United States: The Impact of Increased Molecular Testing

The Journal of Infectious Diseases ◽

10.1093/infdis/jix275 ◽

2017 ◽

Vol 216 (3) ◽

pp. 345-355 ◽

Cited By ~ 22

Author(s):

Claire M Midgley ◽

Amber K Haynes ◽

Jason L Baumgardner ◽

Christina Chommanard ◽

Sara W Demas ◽

...

Keyword(s):

United States ◽

Respiratory Syncytial Virus ◽

The United States ◽

Molecular Testing ◽

Syncytial Virus ◽

The Impact

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Progress in Defining the Role of RSV in Allergy and Asthma: From Clinical Observations to Animal Models

Clinical and Developmental Immunology ◽

10.1080/10446670410001722131 ◽

2004 ◽

Vol 11 (2) ◽

pp. 113-119 ◽

Cited By ~ 22

Author(s):

W. V. Kalina ◽

L. J. Gershwin

Keyword(s):

Animal Models ◽

Rna Virus ◽

Allergic Sensitization ◽

Upper Respiratory Tract ◽

Young Infants ◽

Wide Range ◽

Similar Disease ◽

Rsv Infection ◽

Syncytial Virus ◽

The Impact

Respiratory syncytial virus (RSV), an RNA virus in the family Paramyxoviridae, causes respiratory disease in humans. A closely related bovine RSV is responsible for a remarkably similar disease syndrome in young cattle. Severe RSV disease is characterized by bronchiolitis. The impact of RSV on human health is demonstrated annually when infants are admitted to the hospital in large numbers. Nearly every child will have been infected with RSV by the age of 3 years. While the disease is most severe in young infants and elderly people, it can re-infect adults causing mild upper respiratory tract disease throughout life. In addition, there is growing evidence that RSV infection may also predispose some children to the development of asthma. This is based on the observation that children who wheeze with RSV-induced bronchiolitis are more likely to develop into allergic asthmatics. Recent studies describe attempts to create an RSV induced asthma model in mice and other species; these have shown some degree of success. Such reports of case studies and animal models have suggested a wide range of factors possibly contributing to RSV induced asthma, these include timing of RSV infection with respect to allergen exposure, prior allergic sensitization, environmental conditions, exposure to endotoxin, and the genetic background of the person or animal. Herein, we primarily focus on the influence of RSV infection and inhalation of extraneous substances (such as allergens or endotoxin) on development of allergic asthma.

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