Respiratory Syncytial Virus Antibody Research Articles

Development and validation of a respiratory syncytial virus multiplex immunoassay.

Respiratory syncytial virus (RSV) is one of the leading causes of severe respiratory disease in infants and adults. While vaccines and monoclonal therapeutic antibodies either are or will shortly become available, correlates of protection remain unclear. For this purpose, we developed an RSV multiplex immunoassay that analyses antibody titers toward the post-F, Nucleoprotein, and a diverse mix of G proteins. A bead-based multiplex RSV immunoassay was developed, technically validated to standard FDA bioanalytical guidelines, and clinically validated using samples from human challenge studies. RSV antibody titers were then investigated in children aged under 2 and a population-based cohort. Technical and clinical validation showed outstanding performance, while methodological developments enabled identification of the subtype of previous infections through use of the diverse G proteins for approximately 50% of samples. As a proof of concept to show the suitability of the assay in serosurveillance studies, we then evaluated titer decay and age-dependent antibody responses within population cohorts. Overall, the developed assay shows robust performance, is scalable, provides additional information on infection subtype, and is therefore ideally suited to be used in future population cohort studies.

Respiratory syncytial virus immunoprophylaxis: Novel opportunities and a call for equity.

With the approval of the first vaccines against respiratory syncytial virus (RSV) and a novel RSV-neutralizing antibody, 2023 has been perceived as a game-changing year in preventing severe outcomes of RSV infections in infants and the elderly. However, the costs of these pharmaceuticals are high, while RSV disproportionately impacts populations of low-to-middle-income regions, which may continue to suffer from a lack of pharmaceutical measures for RSV prevention under health and socioeconomic disparities. This paper presents an overview of the characteristics, clinical results, and approval status of various RSV vaccines and anti-RSV antibodies. It posits that wealthy nations cannot monopolize RSV immunoprophylaxis and should work jointly to make it available to lower-income countries. An approach toward RSV immunoprophylaxis equity based on five points is offered: (1) integration of RSV vaccines and antibodies into the existing global humanitarian distribution systems, (2) using affordable RSV vaccine pricing models, (3) enforcing equity as a part of national and global public health strategy, (4) implementing equitable allocation frameworks for RSV immunoprophylaxis, and (5) promoting local manufacturing. Such a plan needs to be put into action as soon as possible to avoid delays in serving the populations with the highest needs related to RSV burden.

Development and comparison of immunologic assays to detect primary RSV infections in infants.

Effective respiratory syncytial virus (RSV) vaccines have been developed and licensed for elderly adults and pregnant women but not yet for infants and young children. The RSV immune state of the young child, i.e., previously RSV infected or not, is important to the conduct and interpretation of epidemiology studies and vaccine clinical trials. To address the need for sensitive assays to detect immunologic evidence of past infection, we developed, characterized, and evaluated 7 assays including 4 IgG antibody enzyme immunoassays (EIAs), two neutralizing antibody assays, and an IFN-γ EliSpot (EliSpot) assay. The four IgG EIAs used a subgroup A plus subgroup B RSV-infected Hep-2 cell lysate antigen (Lysate), an expressed RSV F protein antigen (F), an expressed subgroup A G protein antigen (Ga), or an expressed subgroup B G protein (Gb) antigen. The two neutralizing antibody assays used either a subgroup A or a subgroup B RSV strain. The EliSpot assay used a sucrose cushion purified combination of subgroup A and subgroup B infected cell lysate. All seven assays had acceptable repeatability, signal against control antigen, lower limit of detection, and, for the antibody assays, effect of red cell lysis, lipemia and anticoagulation of sample on results. In 44 sera collected from children >6 months after an RSV positive illness, the lysate, F, Ga and Gb IgG EIAs, and the subgroup A and B neutralizing antibody assays, and the EliSpot assays were positive in 100%, 100%, 86%, 95%, 43%, and 57%, respectively. The Lysate and F EIAs were most sensitive for detecting RSV antibody in young children with a documented RSV infection. Unexpectedly, the EliSpot assay was positive in 9/15 (60%) of PBMC specimens from infants not exposed to an RSV season, possibly from maternal microchimerism. The Lysate and F EIAs provide good options to reliably detect RSV antibodies in young children for epidemiologic studies and vaccine trials.

Research Progress in Respiratory Syncytial Virus Vaccines

In addition to being a substantial source of morbidity and mortality in older persons, respiratory syncytial virus (RSV) is a major contributor to lower respiratory tract infections in newborns and young children. Worldwide, there has been a lot of research done to provide safe and effective vaccinations against this common infection because there isn't an approved RSV vaccine. A succinct summary of current developments in RSV vaccine research is given in this abstract. Many vaccinations have reached the clinical testing stage and shown promising benefits. Live attenuated vaccines, nanoparticle vaccines, and viral vector vaccines are the three primary categories of current vaccination techniques. Additionally, the production of specific RSV antibodies such as MEDI8897 and polyclonal immunoglobulin RI-002 is being evaluated as an important research antibodies for avoiding RSV infection. The continuous dedication to RSV vaccine development gives optimism for the future prevention of RSV-related disorders across all age groups, despite the fact that challenges still exist, particularly ERD (Enhanced respiratory disease).

Loss of Respiratory Syncytial Virus Antibody Functions During the Peak of the COVID-19 Pandemic Mitigation Measures.

Studies have linked RSV antibody-mediated phagocytosis and complement deposition to severe RSV infection. We show waning of these functions in women of childbearing age during 2020-2021 and implementation of COVID-19 mitigation measures and RSV hiatus. These functions may be explored as immune correlates of protection against RSV.

Optimal site of care for administration of extended half-life respiratory syncytial virus (RSV) antibodies to infants in the United States (US)

IntroductionNew extended half-life antibodies for the single-dose prevention of medically attended (MA) respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) have been developed for administration to all infants before or during their first RSV season. For infants born during the season, administration as soon as feasible after birth would provide optimal protection and minimize access disparities.The objective of this study was to assess the time from birth hospitalization discharge to the first outpatient visit (FOV) among US infants in order to determine optimal site of administration for the extended half-life antibody. Material and methodsThis retrospective, observational, time-to-event analysis uses the Merative™ MarketScan® Commercial and Multi-State Medicaid Databases. Time to FOV is reported separately for the COVID-19 and recent pre-COVID-19 eras and for commercially insured and Medicaid infants. ResultsOverall, 73.8 % of Medicaid infants had an FOV within 5 days as compared to 84.7 % of commercially insured infants. Estimates were higher during the COVID-19 era. Urban commercially insured infants had much higher FOV completion than their counterparts. Among Medicaid infants, urban Black and rural White infants were least likely to complete their FOV within 5 days of birth hospitalization discharge. Discussion and conclusionFOV within 5 days after birth hospitalization discharge for Medicaid infants is substantially lower than that of commercially insured infants. Approximately 1 in 4 Medicaid infants and 1 in 8 infants with commercial insurance did not have an outpatient visit within 5 days of birth hospitalization discharge. For US infants born during the RSV season, administration of extended half-life RSV antibodies in the newborn nursery prior to discharge would ensure optimal uptake and minimize access disparities.

Durability of neutralizing RSV antibodies following nirsevimab administration and elicitation of the natural immune response to RSV infection in infants

Nirsevimab is an extended half-life monoclonal antibody specific for the prefusion conformation of the respiratory syncytial virus (RSV) F protein, which has been studied in preterm and full-term infants in the phase 2b and phase 3 MELODY trials. We analyzed serum samples collected from 2,143 infants during these studies to characterize baseline levels of RSV-specific immunoglobulin G antibodies and neutralizing antibodies (NAbs), duration of RSV NAb levels following nirsevimab administration, the risk of RSV exposure during the first year of life and the infant’s adaptive immune response to RSV following nirsevimab administration. Baseline RSV antibody levels varied widely; consistent with reports that maternal antibodies are transferred late in the third trimester, preterm infants had lower baseline RSV antibody levels than full-term infants. Nirsevimab recipients had RSV NAb levels >140-fold higher than baseline at day 31 and remained >50-fold higher at day 151 and >7-fold higher at day 361. Similar seroresponse rates to the postfusion form of RSV F protein in nirsevimab recipients (68–69%) compared with placebo recipients (63–70%; not statistically significant) suggest that while nirsevimab protects from RSV disease, it still allows an active immune response. In summary, nirsevimab provided sustained, high levels of NAb throughout an infant’s first RSV season and prevented RSV disease while allowing the development of an immune response to RSV.

A human antibody potently neutralizes RSV by targeting the conserved hydrophobic region of prefusion F.

Respiratory syncytial virus (RSV) continues to pose serious threats to pediatric populations due to the lack of a vaccine and effective antiviral drugs. RSV fusion (F) glycoprotein mediates viral-host membrane fusion and is a key target for neutralizing antibodies. We generated 23 full-human monoclonal antibodies (hmAbs) against prefusion F protein (pre-F) from a healthy adult with natural RSV infection by single B cell cloning technique. A highly potent RSV-neutralizing hmAb, named as 25-20, is selected, which targets a new site Ø-specific epitope. Site-directed mutagenesis and structural modelling analysis demonstrated that 25-20 mainly targets a highly conserved hydrophobic region located at the a4 helix and a1 helix of pre-F, indicating a site of vulnerability for drug and vaccine design. It is worth noting that 25-20 uses an unreported inferred germline (iGL) that binds very poorly to pre-F, thus high levels of somatic mutations are needed to gain high binding affinity with pre-F. Our observation helps to understand the evolution of RSV antibody during natural infection. Furthermore, by in silico prediction and experimental verification, we optimized 25-20 with KD values as low as picomolar range. Therefore, the optimized 25-20 represents an excellent candidate for passive protection against RSV infection.

Antibody-based protection against respiratory syncytial virus in mice and their offspring through vectored immunoprophylaxis.

Respiratory syncytial virus (RSV) causes acute lower respiratory tract infections, with potential lower respiratory tract infections, which can be particularly problematic in infants and the elderly. There are no approved vaccines for RSV. The current standard of care for high-risk individuals is monthly administration of palivizumab, a humanized murine monoclonal antibody (mAb) targeting the RSV fusion protein. Adeno-associated virus (AAV)-mediated expression of mAbs has previously led to sustained expression of therapeutic concentrations of mAbs in several animal models, representing an alternative to repetitive passive administration. Intramuscular (IM) administration of AAV6.2FF expressing RSV antibodies, palivizumab or hRSV90, resulted in high concentrations of human (h)IgG1 mAbs in the serum and at various mucosal surfaces, while intranasal administration limited hIgG expression to the respiratory tract. IM administration of AAV6.2FF-hRSV90 or AAV6.2FF-palivizumab in a murine model provided sterilizing immunity against challenge with RSV A2. Evidence of maternal passive transfer of vectorized hRSV90 was detected in both murine and ovine models, with circulating mAbs providing sterilizing immunity in mouse progeny. Finally, addition of a "kill switch" comprised of LoxP sites flanking the mAb genes resulted in diminished serum hIgG after AAV-DJ-mediated delivery of Cre recombinase to the same muscle group that was originally transduced with the AAV-mAb vector. The ability of this AAV-mAb system to mediate robust, sustained mAb expression for maternal transfer to progeny in murine and ovine models emphasizes the potential of this platform for use as an alternative prophylactic vaccine for protection against neonatal infections, particularly in high-risk infants.

High seroprevalence of antibodies against human respiratory syncytial virus and evidence of respiratory syncytial virus reinfection in young children in Thailand

ObjectivesTo investigate the seroprevalence of respiratory syncytial virus (RSV) infections in young children, the correlation between RSV antibody levels in maternal and cord serum, and to provide evidence of RSV reinfection in Thai children after primary infections. MethodsSerum samples were collected from 302 mothers and 291 children between 2015 and 2021. Maternal and cord blood were collected at birth. Serial serum samples of children were collected at the ages of 2, 7, 18, 19, 24, 36, 48, and 60 months and the presence of anti-RSV immunoglobulin G (IgG) was tested using an enzyme-linked immunosorbent assay. ResultsThe cord: maternal serum antibody ratio was 1.09 (95% confidence interval 1.08-1.11). Although >90% of babies at birth were seropositive through transplacental transfer, antibody levels gradually declined, with the highest seronegative rate (91.9%) at 7 months of age. Subsequently, anti-RSV IgG levels increased with age, most likely due to natural infection. One-third of the children showed evidence of reinfection as determined by seroconversion of anti-RSV IgG or increased titers of at least 50 relative units/ml. ConclusionWaning of RSV antibodies in infants is rapid, and RSV infection subsequently increases anti-RSV IgG titers. RSV vaccination in children before the age of 7 months should be recommended.

A Pan-Pneumovirus vaccine based on immunodominant epitopes of the fusion protein.

Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are two leading causes of severe respiratory infections in children, the elderly, and immunocompromised patients. The fusion (F) protein is the major target of neutralizing antibodies. Recent developments in stabilizing the pre-fusion conformation of the F proteins, and identifying immunodominant epitopes that elicit potent neutralizing antibodies have led to the testing of numerous pre-fusion RSV F-based vaccines in clinical trials. We designed and tested the immunogenicity and protective efficacy of a chimeric fusion protein that contains immunodominant epitopes of RSV F and hMPV F (RHMS-1). RHMS-1 has several advantages over vaccination with pre-fusion RSV F or hMPV F, including a focus on recalling B cells to the most important protective epitopes and the ability to induce protection against two viruses with a single antigen. RHMS-1 was generated as a trimeric recombinant protein, and analysis by negative-stain electron microscopy demonstrated the protein resembles the pre-fusion conformation. Probing of RHMS-1 antigenicity using a panel of RSV and hMPV F-specific monoclonal antibodies (mAbs) revealed the protein retains features of both viruses, including the pre-fusion site Ø epitope of RSV F. Mice immunized with RHMS-1 generated neutralizing antibodies to both viruses and were completely protected from RSV or hMPV challenge. Overall, this study demonstrates protection against two viruses with a single antigen and supports testing of RHMS-1 in additional pre-clinical animal models.

Correlates of Protection Against Respiratory Syncytial Virus Infection in Infancy.

The highest morbidity and mortality from respiratory syncytial virus (RSV) infection occurs in young infants. Immunization of expectant mothers during pregnancy has the potential to substantially reduce the burden of RSV disease in a majority of infants. Correlates of protection (COP) are important in guiding the development of maternal RSV vaccines and the design of maternal RSV vaccine trials, as immune response to candidate vaccines should mirror protective RSV immunity at birth. Here, we review the literature reporting correlations between RSV immune measures at birth and clinical RSV outcomes during infancy. Less than a dozen studies have investigated immunological COP with RSV disease or related hospitalization, yielding inconsistent findings overall. The differences in findings between studies could be due to differences in inclusion/exclusion criteria (e.g., the inclusion of older infants who may benefit less from maternal antibodies or infants followed during inter-seasonal periods where RSV is absent), differences in semi-quantitative RSV antibody neutralization assays, or differences in RSV outcome measures such as the sensititivity/specificity of diagnostic tests. Future research in this field should seek to standardize RSV immunological measures and outcomes, expand the breadth of functional RSV measures beyond antibody neutralization, and consider infants' age and seasonality of RSV infection.

Waning Immunity Against Respiratory Syncytial Virus During the Coronavirus Disease 2019 Pandemic.

Health jurisdictions have seen a near-disappearance of Respiratory Syncytial Virus (RSV) during the first year of the COVID-19 pandemic. Over a corresponding period, we report a reduction in RSV antibody levels and neutralization in women and infants one year into the COVID-19 pandemic (February – June 2021) compared to earlier in the pandemic (May – June 2020), in British Columbia (BC), Canada. This supports that humoral immunity against RSV is relatively short-lived and its establishment in infants requires repeated viral exposure. Waned immunity in young children may explain the inter-seasonal resurgence of RSV cases in BC as seen also in other countries.

Transplacental transfer of RSV antibody in Australian First Nations infants.

Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory infection hospitalisations in Aboriginal infants specifically those aged <6 months. Maternally derived RSV antibody (Ab) can protect against severe RSV disease in infancy. However, the efficiency of transplacental transfer of maternal anti-RSV Ab remains unknown in Aboriginal infants. We characterised RSV Ab in Australian First Nations mother-infant pairs (n = 78). We investigated impact of covariates including low birthweight, gestational age (GA), sex of the baby, maternal age and multiparity of the mother on cord to maternal anti-RSV Ab titre ratio (CMTR) using multivariable logistic regression model. All (n = 78) but one infant was born full term (median GA: 39 weeks, interquartile range: 38–40 weeks) and 56% were males. The mean log2 RSV Ab titre was 10.7 (SD ± 1.3) in maternal serum and 11.0 (SD ± 1.3) in cord serum at birth; a ratio of 1.02 (SD ±0.06). One-third of the pairs had a CMTR of <1 indicating impaired transfer. Almost 9% (7/78) of the term infants had cord RSV Ab levels below <log2 9. Covariates showed no effect on CMTR. Further mechanistic research is needed to determine the significance of these findings on RSV disease in First Nations children.

Cord-blood respiratory syncytial virus antibodies and respiratory health in first 5 years of life.

To determine the potential longer-term effects of maternal antenatal respiratory syncytial virus (RSV) vaccination, we examined the association between cord-blood RSV-neutralizing antibodies (RSV-NA) and RSV infections in the first 2 years of life, RSV-NA at 3 years, and respiratory health to age 5 years. Two community-based Australian birth cohorts were combined. For children with at least one atopic parent, paired serum RSV-NA levels were compared in cord blood and at age 3 years. Weekly nasal swabs were collected in one cohort and during acute respiratory infections (ARI) in the other. Wheeze history up to age 5 years and physician-diagnosed asthma at 5 years was collected by parent report. In 264 children, each log10 increase of cord-blood RSV-NA level was associated with 37% decreased risk (adjusted incidence-rate-ratio [aIRR] 0.63; 95% confidence interval [CI]: 0.40-1.01) of RSV-ARI and 49% decreased risk (aIRR 0.51; 95% CI: 0.25-1.02) of RSV acute lower respiratory infections (ALRI) at 12-24 months of age. However, higher cord-blood RSV-NA was associated with increased risk of all-cause ALRI (aIRR 1.29; 95% CI: 0.99-1.69), wheeze-associated ALRI (aIRR 1.75; 95% CI: 1.08-2.82), and severe ALRI (aIRR 2.76; 95% CI: 1.63-4.70) at age 6-<12 months. Cord-blood RSV-NA was not associated with RSV-ARI in the first 6-months, RSV-NA levels at 3 years, or wheeze or asthma at 5 years. Higher levels of cord-blood RSV-NA did not protect against RSV infections during the first 6-months-of-life, time-to-first RSV-ARI, or wheeze or asthma in the first 5 years of life. Additional strategies to control RSV-related illness in childhood are needed.

Humoral and Mucosal Antibody Response to RSV Structural Proteins in RSV-Infected Adult Hematopoietic Cell Transplant (HCT) Recipients.

Respiratory syncytial virus (RSV) is an important cause of lower respiratory tract infection in infants, the elderly, and immunocompromised patients. RSV antibodies play a role in preventing reinfection and in clearance of RSV, but data regarding the levels of viral protein-specific antibodies elicited and their contribution to patient recovery from RSV-induced disease are limited. We prospectively enrolled a cohort of RSV-infected adult hematopoietic cell transplant (HCT) recipients (n = 40). Serum and nasal-wash samples were obtained at enrollment (acute samples) and convalescence (convalescent samples). We measured (1) humoral IgG and mucosal IgA binding antibody levels to multiple RSV proteins (F, G, N, P, and M2-1) by Western blot (WB); (2) neutralizing antibody (Nt Ab) titers by microneutralization assay; and (3) palivizumab-like antibody (PLA) concentrations by an ELISA-based competitive binding assay developed in the lab. Finally, we tested for correlations between protein-specific antibody levels and duration of viral shedding (normal: cleared in <14 days and delayed: cleared ≥14 days), as well as RSV/A and RSV/B subtypes. Convalescent sera from HCT recipients had significantly higher levels of anti-RSV antibodies to all 5 RSV structural proteins assayed (G, F, N, P, M2-1), higher Nt Abs to both RSV subtypes, and higher serum PLAs than at enrollment. Significantly higher levels of mucosal antibodies to 3 RSV structural proteins (G, N, and M2-1) were observed in the convalescent nasal wash versus acute nasal wash. Normal viral clearance group had significantly higher levels of serum IgG antibodies to F, N, and P viral proteins, higher Nt Ab to both RSV subtypes, and higher PLA, as well as higher levels of mucosal IgA antibodies to G and M2-1 viral proteins, and higher Nt Ab to both RSV subtypes compared to delayed viral clearance group. Normal RSV clearance was associated with higher IgG serum antibody levels to F and P viral proteins, and PLAs in convalescent serum (p < 0.05). Finally, overall antibody levels in RSV/A- and/B-infected HCT recipients were not significantly different. In summary, specific humoral and mucosal RSV antibodies are associated with viral clearance in HCT recipients naturally infected with RSV. In contrast to the humoral response, the F surface glycoprotein was not a major target of mucosal immunity. Our findings have implications for antigen selection in the development of RSV vaccines.

A prospective surveillance study on the kinetics of the humoral immune response to the respiratory syncytial virus fusion protein in adults in Houston, Texas

Respiratory syncytial virus (RSV)-specific serum antibody has been correlated to protection of infection and reduction of severe disease, but reinfection is still frequent. In this study, we evaluated RSV-specific serum antibody activity following natural RSV re-infection to examine the longevity of the humoral immune response in adults. Nineteen healthy adult volunteers under sixty-five years of age were enrolled during the 2018–2019 RSV season in Houston, TX. Blood was collected at three study visits. The kinetics of RSV-neutralizing, RSV F site-specific competitive, and RSV-binding antibodies in serum samples were measured by microneutralization and enzyme-linked immunosorbent assays. Three distinct profiles of RSV-specific antibody kinetics were identified that were consistent with RSV infection status: uninfected, acutely infected, and recently infected. The uninfected group had stable antibody titers for the duration of the study period (185 days). The acutely infected group had lower antibody responses at the beginning of the study, supporting a correlate of infection, followed by a significant antibody response after infection that was maintained for at least 125 days. Unlike the acutely infected group, the recently infected group had a significant precipitous decrease in RSV antibody in only 60 days. This study is the first, to our knowledge, to describe this abrupt loss of RSV-specific antibody in detail. This rapid decline of antibody may present an obstacle for the development of vaccines with lasting protection against RSV, and perhaps other respiratory pathogens. Neutralizing antibody responses were greater to prototypic than contemporaneous RSV strains, regardless of infection status, indicating that original antigenic sin may impact the humoral immune response to new or emerging RSV strains.

Clinico demographic profiling of the Respiratory syncytial virus (RSV) infected children admitted in tertiary care hospital in North India.

Background:Acute bronchiolitis is fatal disease involving lower respiratory tract of infants and children of paediatric age group. Respiratory Syncytial Virus (RSV) is responsible for causing more than 70% hospital admissions of children aged less than 2 years thus making a necessity for accurate and timely diagnosis.Aims:The main aim of study was clinicodemographic correlation of RSV positive children presenting to our tertiary care hospital.Setting and Design:It is a retrospective study done between December to January 2018.Materials and Methods:Detection of RSV antigen from nasophyrangeal aspirates using Mouse Monoclonal anti RSV Antibody (by Novatetra) and Goat Anti Mouse Antibody conjugated with FITC as secondary antibody.Results:A total of 147 samples were received in the laboratory and 20 were tested as positive for RSV Antigen. Totally, 19/20 children were aged less than 1 year and with a male predominance. The most common symptom was cough and respiratory distress. Eight percent of the children showed wheezing and 18/20 required assisted ventilation. The clinical course in one child deteriorated leading to death of that patient.Conclusions:The timely diagnosis and management of RSV infected children is utmost needed to prevent morbidity and mortality. The premorbid conditions can assist to differentiate the viral from bacterial pneumonia and thus enable speedy recovery of the child.

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

BackgroundRespiratory 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.MethodsWe 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.ResultsMaternal 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.ConclusionsMaternally 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.

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

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. 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. 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. 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.