Stabilized trimeric peptide immunogens of the complete HIV-1 gp41 N-heptad repeat and their use as HIV-1 vaccine candidates.

Efforts to develop an HIV-1 vaccine include those focusing on conserved structural elements as the target of broadly neutralizing monoclonal antibodies. MAb D5 binds to a highly conserved hydrophobic pocket on the gp41 N-heptad repeat (NHR) coiled coil and neutralizes through prevention of viral fusion and entry. Assessment of 17-mer and 36-mer NHR peptides presenting the D5 epitope in rodent immunogenicity studies showed that the longer peptide elicited higher titers of neutralizing antibodies, suggesting that neutralizing epitopes outside of the D5 pocket may exist. Although the magnitude and breadth of neutralization elicited by NHR-targeting antigens are lower than that observed for antibodies directed to other epitopes on the envelope glycoprotein complex, it has been shown that NHR-directed antibodies are potentiated in TZM-bl cells containing the FcγRI receptor. Herein, we report the design and evaluation of covalently stabilized trimeric 51-mer peptides encompassing the complete gp41 NHR. We demonstrate that these peptide trimers function as effective antiviral entry inhibitors and retain the ability to present the D5 epitope. We further demonstrate in rodent and nonhuman primate immunization studies that our 51-mer constructs elicit a broader repertoire of neutralizing antibody and improved cross-clade neutralization of primary HIV-1 isolates relative to 17-mer and 36-mer NHR peptides in A3R5 and FcγR1-enhanced TZM-bl assays. These results demonstrate that sensitive neutralization assays can be used for structural enhancement of moderately potent neutralizing epitopes. Finally, we present expanded trimeric peptide designs which include unique low-molecular-weight scaffolds that provide versatility in our immunogen presentation strategy.

Selective effects of estradiol on human corneal endothelial cells.

In Fuchs endothelial corneal dystrophy (FECD), mitochondrial and oxidative stresses in corneal endothelial cells (HCEnCs) contribute to cell demise and disease progression. FECD is more common in women than men, but the basis for this observation is poorly understood. To understand the sex disparity in FECD prevalence, we studied the effects of the sex hormone 17-ß estradiol (E2) on growth, oxidative stress, and metabolism in primary cultures of HCEnCs grown under physiologic ([O2]2.5) and hyperoxic ([O2]A) conditions. We hypothesized that E2 would counter the damage of oxidative stress generated at [O2]A. HCEnCs were treated with or without E2 (10 nM) for 7-10 days under both conditions. Treatment with E2 did not significantly alter HCEnC density, viability, ROS levels, oxidative DNA damage, oxygen consumption rates, or extracellular acidification rates in either condition. E2 disrupted mitochondrial morphology in HCEnCs solely from female donors in the [O2]A condition. ATP levels were significantly higher at [O2]2.5 than at [O2]A in HCEnCs from female donors only, but were not affected by E2. Our findings demonstrate the resilience of HCEnCs against hyperoxic stress. The effects of hyperoxia and E2 on HCEnCs from female donors suggest cell sex-specific mechanisms of toxicity and hormonal influences.

The efficacy of 2 different phakic intraocular lens implant in keratoconus as an isolated procedure or combined with collagen crosslinking and intra-stromal corneal ring segments: a systematic review and meta-analysis.

PURPOSE: To compare the efficacy of phakic intra-ocular lenses in isolation or in combination with corneal crosslinking (CXL) and/or intra-stromal corneal ring segments (ICRS) in keratoconus. METHODS: Data extracted from the publications meeting the selection. The outcome parameters included mean pre- and post-operative uncorrected distance visual acuity, corrected distance visual acuity (CDVA), sphere and cylinder of refraction and complications. Available data analyzed with Cochrane Review Manager. RESULTS: A total of 23 studies including 464 eyes were included. All the parameters showed significant improvement in all subgroups other than CDVA in ACPIOL + CXL subgroup and cylinder in PIOL + CXL subgroups. There was not a significant difference between PCPIOL and ACPIOL in the outcomes, exception was more improvement of CDVA in "ACPIOL only" than" PCPIOL only" subgroup. CONCLUSION: Both PCPIOLs and ACPIOLs are comparably safe and efficient options in management of KCN and their efficacy significantly improves when combined with CXL/ICRS.

Selective effects of estradiol on human corneal endothelial cells.

Fuchs endothelial corneal dystrophy (FECD) results from genetic and environmental factors triggering mitochondrial and oxidative stress in corneal endothelial cells (CEnCs) leading to CEnC death and corneal opacification. FECD is more common in women than men, but the basis for this observation is unknown. Because FECD is commonly diagnosed around the time of the menopausal transition in women when estrogen levels decrease precipitously, we studied the effects of the potent estrogen,17-ß estradiol (E2) on growth, oxidative stress, and metabolism in primary cultures of human CEnCs (HCEnCs) under conditions of physiologic 2.5% O 2 ([O 2 ] 2.5 ) and under hyperoxic stress ([O 2 ] A : room air + 5% CO 2 ). We hypothesized that E2 would counter the stresses of the hyperoxic environment in HCEnCs. HCEnCs were treated ± 10 nM E2 for 7-10 days at [O 2 ] 2.5 and [O 2 ] A followed by measurements of cell density, viability, reactive oxygen species (ROS), mitochondrial morphology, oxidative DNA damage, ATP levels, mitochondrial respiration (O 2 consumption rate [OCR]), and glycolysis (extracellular acidification rate [ECAR]). There were no significant changes in HCEnC density, viability, ROS levels, oxidative DNA damage, OCR, and ECAR in response to E2 under either O 2 condition. We found that E2 disrupted mitochondrial morphology in HCEnCs from female donors but not male donors at the [O 2 ] A condition. ATP levels were significantly higher at [O 2 ] 2.5 compared to [O 2 ] A in HCEnCs from female donors only, but were not affected by E2. Our findings demonstrate the overall resilience of primary HCEnCs against hyperoxic stress. The selective detrimental effects of hyperoxia and estradiol on HCEnCs from female but not male donors suggests mechanisms of toxicity based upon cell-sex in addition to hormonal environment.

Risk assessment of variant Creutzfeldt-Jakob disease in corneal transplantation.

Purpose: While corneal transplantation is known to have a potential risk of transmission of variant Creutzfeldt-Jacob Disease (vCJD), the magnitude of this risk has not been quantified. Observations: A case report is presented of a 73 year-old man with a penetrating keratoplasty graft from corneal tissue that was recalled after transplantation due to risk of vCJD because it was later discovered that the donor had traveled to the United Kingdom (UK). Probabilities of vCJD transmission were extrapolated using Creutzfeldt-Jacob Disease (CJD) mortality (incidence) rate, all-cause death rate, and rate of recovery for intended transplantation. Conclusions: An overestimate of the risk of transplanting a cornea infected with vCJD in 2018 was 1 in 940,000. The true risk of vCJD transmission would be even lower due to an incomplete infectivity rate. We conclude that the risk of transmission of latent vCJD by corneal transplantation from a donor who traveled to the UK from 1980 to 1996 is exceedingly low.

Efficacy of skin-to-skin vs. cloth-to-cloth contact for thermoregulation in low birth weight newborns: a randomized crossover trial.

OBJECTIVE: Skin-to-skin contact (SSC) is effective to maintain normal temperature in low birth weight (LBW) newborns. However, there are several barriers related to privacy and space availability for its optimum utilization. We used cloth-to-cloth contact (CCC), i.e. placing the newborn in Kangaroo position without removing cloths as an innovative alternative to SSC to test its efficacy for thermoregulation and feasibility as compared to SSC in LBW newborns. METHODS: The newborns eligible for Kangaroo Mother Care (KMC) in step-down nursery were included in this randomized crossover trial. Newborns received SSC or CCC as per randomization on the first day and then crossed over to other group on the next day and so on. A feasibility questionnaire was asked to the mothers and the nurses. Axillary temperature was measured at various time intervals. Group comparisons were made by either using independent sample t-test or Chi-square test. RESULTS: A total of 23 newborns received KMC for total 152 occasions in the SSC group and 149 times in the CCC group. There was no significant temperature difference between the groups at any time-point. Mean (standard deviation) gain of temperature at 120 min in the CCC group [0.43 (0.34)°C] was comparable to the SSC group [0.49 (0.36)°C] (p = 0.13). We did not observe any adverse effect of CCC. Most mothers and nurses perceived CCC feasible in hospital settings and felt that it could be feasible in-home settings too. CONCLUSION: CCC was safe, more feasible and not inferior to SSC for maintaining thermoregulation in LBW newborns.

Skin-to-skin contact (SSC) helps in maintaining optimum temperature of low birth weight (LBW) newborns. It is an important component of Kangaroo Mother Care (KMC), which is standard of care and reduces several neonatal morbidities and mortality. However, there are several barriers for the optimum utilization of KMC. One of the major barriers is privacy issues while putting newborn in SSC. To overcome this barrier for increasing KMC uptake, we innovatively thought of keeping the newborn on mother's chest without removing the cloths of both the mother and the newborn. We called it cloth-to-cloth contact (CCC). We compared SSC and CCC for temperature regulation in the newborns weighing between 1500 and 2499 g at the time of enrollment using a crossover design. We observed that mean temperature steadily increased in newborns while receiving SSC or CCC for 2 h. There were no significant differences in mean temperature readings between these two groups at various time points. Thus, CCC was not inferior to SSC in maintaining temperature. We did not observe any adverse effect of CCC. CCC may overcome the barrier of privacy issues of SSC. Thus, CCC was equally efficacious, safe and more feasible for maintaining thermoregulation in LBW newborns.

The soil and the seed: The relationship between Descemet's membrane and the corneal endothelium.

Descemet's membrane (DM), the basement membrane of the corneal endothelium, is formed from the extracellular matrix (ECM) secreted by corneal endothelial cells. The ECM supports the growth and function of the corneal endothelial cells. Changes to DM are central to the diagnosis of the most common corneal endothelial disease, Fuchs endothelial corneal dystrophy (FECD). Changes in DM are also noted in systemic diseases such as diabetes mellitus. In FECD, the DM progressively accumulates guttae, "drop-like deposits" that disrupt the corneal endothelial cell monolayer. While the pathophysiologic changes to corneal endothelial cells in the course of FECD have been well described and reviewed, the changes to DM have received limited attention. The reciprocity of influence between the corneal endothelial cells and DM demands full attention to the latter in our search for novel treatment and preventive strategies. In this review, we discuss what is known about the formation and composition of DM and how it changes in FECD and other conditions. We review characteristics of guttae and the interplay between corneal endothelial cells and guttae, particularly as it might apply to future cell-based and genetic therapies for FECD.

Recurrence of Herpetic Keratitis after COVID-19 Vaccination: A Report of Two Cases.

Background: Recurrence of herpetic keratitis following vaccination has been documented following vaccination with the Zostavax, trivalent flu, hepatitis A, and rabies vaccines. The USFDA and WHO have acknowledged that the novel COVID-19 vaccines similarly have a risk of reactive immunologic-based inflammation, namely, myositis, pericarditis, and Guillain-Barré syndrome. Case Presentation. We present two patients with latent herpetic keratitis who experienced reactivation of keratitis within weeks of COVID-19 vaccination despite prolonged periods of prior latency. A 52-year-old healthy male with no herpes simplex virus (HSV) keratitis recurrences in two years developed visual decline and patchy stromal haze within 24-48 hours of receiving the second Pfizer-BioNTech (COVID-19 BNT162b2) vaccine. A 67-year-old female with chronic neurotrophic keratitis developed her most severe exacerbation of herpes zoster keratitis in over 10 years occurring 2-3 weeks after her first Moderna (mRNA-1273) vaccine, which was later complicated by bacterial superinfection. Conclusions: The COVID-19 vaccines work by generating both adaptive humoral and cellular immune responses in humans, including elevation of anti-spike neutralizing antibody titers, antigen-specific CD4+ and CD8+ T-cell responses, and increased levels of proinflammatory cytokines such as interferon gamma (IFNγ). The general activation of the T-cell-mediated immune response and proinflammatory cytokines such as IFNγ may underlie the role of the COVID vaccines in reactivation of herpetic stromal keratitis and the clinical findings in our reported cases.

Baseline Assessment of Evidence-Based Intrapartum Care Practices in Medical Schools in 3 States in India: A Mixed-Methods Study.

INTRODUCTION: Implementation research with pre- and post-comparison was planned to improve the quality of evidence-based intrapartum care services in Indian medical schools. We present the baseline study results to assess the status of adherence to intrapartum evidence-based practices (IP-EBP) in study schools in 3 states in India and the perception of the faculty. METHODS: A concurrent mixed-methods approach was used to conduct the baseline assessment in 9 medical schools in Rajasthan, Gujarat, and Union Territory from October 2018 to June 2019. IP-EBP among pregnant women in uncomplicated first (n=135), second (n=120), and third stage (n=120) of labor were observed using a predesigned, pretested checklist quantitatively. We conducted in-depth interviews with 33 obstetrics and gynecology faculty to understand their perceptions of intrapartum practices. Quantitative data were analyzed using SPSS (version 22). COM-B (Capability, Opportunity, and Motivation Behavior) model was used to understand the behaviors, and thematic analysis was done for the qualitative data. FINDINGS: Unindicated augmentation of labor was done in 64.4%, fundal pressure applied in 50.8%, episiotomy done in 58.3%, and delivery in lithotomy position was performed in 86.7% of women in labor. CONCLUSIONS: Intrapartum practices that are not recommended were routinely practiced in the study medical schools due to a lack of staff awareness of evidence-based practices and incorrect beliefs about their impact.

Effect of Physiological Oxygen on Primary Human Corneal Endothelial Cell Cultures.

PURPOSE: Primary human corneal endothelial cells (HCEnCs) cultured in room air are exposed to significantly higher O2 concentrations [O2] than what is normally present in the eye. We evaluated the growth and metabolism of HCEnCs cultured under physiological [O2] (2.5%; [O2]2.5) and room air ([O2]A). METHODS: Primary cultures of HCEnCs from normal donors and donors with Fuchs dystrophy were grown at [O2]2.5 and [O2]A. Growth and morphology were compared using phase-contrast microscopy, zonula occludens (ZO-1) localization, cell density measurements, and senescence marker staining. CD44 (cell quality) and HIF-1α (hypoxia-inducible factor-1α) levels were evaluated by Western blotting. Cell adaptability to a reversal of [O2] growth conditions was measured with cell viability assays, and cell metabolism was assessed via oxygen consumption and extracellular acidification rates. RESULTS: HCEnCs grown at [O2]A and [O2]2.5 displayed similar morphologies, ZO-1 localization, CD44 expression, and senescence. Cells from donors with Fuchs dystrophy grew better at [O2]2.5 than at [O2]A. HIF-1α was undetectable. Cells displayed greater viability at [O2]2.5 than at [O2]A. HCEnCs showed significantly greater proton leak (P < 0.01), nonmitochondrial oxygen consumption (P < 0.01), and spare capacity (P < 0.05) for oxygen consumption rates, and greater basal glycolysis (P < 0.05) with a decreased glycolytic reserve capacity (P < 0.05) for extracellular acidification rates. CONCLUSIONS: Primary HCEnCs show unique metabolic characteristics at physiologic [O2]. The effect of [O2] for optimization of HCEnC culture conditions should be considered. TRANSLATIONAL RELEVANCE: With the advance of cell-based therapeutics for corneal endothelial diseases, [O2] should be considered an important variable in the optimization of HCEnC culture conditions.

A portable, low-cost practice model for microsurgical skills training.

PURPOSE: We describe a portable practice model for acquisition of microsurgical skills using widely available inexpensive tools and materials as a model in learning ophthalmic corneal suturing skills. METHODS: Interested participants without prior microsurgery experience affiliated with the Jacobs School of Medicine and Biomedical Sciences with no prior microsurgical experience qualified to participate. Each participant completed written informed consent. We developed a 3-dimensional micro-stellated icosahedron model using microtubules, monofilament fishing line, jewelers' forceps, and a basic laboratory dissection microscope. We tested this model in improving microsurgical skills in a randomized, controlled intervention trial. Following a pre-assessment task of passing a microsurgical needle and performing a tie, participants were randomized to a control or an intervention (building the micro-stellated icosahedrons) group. The assessment task was repeated after two weeks. Videos of pre- and post-assessments were rated by two masked ophthalmologists. Technique scores and time to complete microsurgical tasks were analyzed to determine improvement in skills. RESULTS: A total of 27 microsurgically naïve participants were recruited and randomized (14 Intervention / 13 Control). Comparing pre- and post-assessments, the intervention group showed significant decrease in time required to pass the needle (P = 0.018) and significant improvement in technical scores. (P = 0.001). In the control group, there was no significant decrease in time or improvement in technical scores. CONCLUSIONS: The portable inexpensive micro-stellated icosahedron skills acquisition model is an effective practice model to acquire skills necessary to perform a microsurgical tie. The similarity in dimensions between the model and the eye suggests translatability to ophthalmic surgery.

Redefining the Histone Deacetylase Inhibitor Pharmacophore: High Potency with No Zinc Cofactor Interaction.

A novel series of histone deacetylase (HDAC) inhibitors lacking a zinc-binding moiety has been developed and described herein. HDAC isozyme profiling and kinetic studies indicate that these inhibitors display a selectivity preference for HDACs 1, 2, 3, 10, and 11 via a rapid equilibrium mechanism, and crystal structures with HDAC2 confirm that these inhibitors do not interact with the catalytic zinc. The compounds are nonmutagenic and devoid of electrophilic and mutagenic structural elements and exhibit off-target profiles that are promising for further optimization. The efficacy of this new class in biochemical and cell-based assays is comparable to the marketed HDAC inhibitors belinostat and vorinostat. These results demonstrate that the long-standing pharmacophore model of HDAC inhibitors requiring a metal binding motif should be revised and offers a distinct class of HDAC inhibitors.

Relationship of Body Mass Index With Fuchs Endothelial Corneal Dystrophy Severity and TCF4 CTG18.1 Trinucleotide Repeat Expansion.

PURPOSE: To investigate the association of body mass index (BMI) with Fuchs endothelial corneal dystrophy (FECD) severity and TCF4 CTG18.1 expansion. METHODS: A total of 343 patients with FECD were enrolled from the Mayo Clinic. FECD severity was graded by slit-lamp biomicroscopy. BMI values were obtained from the electronic medical records. DNA extracted from leukocytes was analyzed for CTG18.1 expansion length, with ≥40 repeats considered expanded. Wilcoxon signed-rank tests were used to compare FECD grade and CTG18.1 expansion length in patients by BMI (<25, ≥25 to <30, and ≥30 kg/m2). FECD grade was regressed on age, sex, BMI, and CTG18.1 expansion and, separately, BMI on CTG18.1 expansion. Models were investigated for effect modification by age and sex with an interaction term of P < 0.05 considered statistically significant. RESULTS: When examining the association between BMI and FECD, there was a significant interaction between BMI and sex (P for interaction = 0.004). When controlling for age and CTG18.1 expansion, a positive association was observed between BMI and FECD grade in women, but not in men. In addition, BMI was not associated with CTG18.1 expansion when controlling for age and sex. CONCLUSIONS: BMI was positively associated with FECD severity among women but not men. There was no significant association between BMI and CTG18.1 expansion. These findings suggest that increased BMI is potentially a modifiable risk factor for FECD disease progression among women.

Posterior pole retinal thickness distribution pattern in keratoconus.

PURPOSE: To evaluate the pattern of retinal thickness distribution in patients with keratoconus (KCN) and its correlation with disease severity. METHODS: For this cross-sectional cohort study, the study subjects with documented keratoconus and normal eyes were prospectively enrolled. All subjects had anterior segment (Pentacam HR) and posterior segment (Spectralis) imaging. Posterior segment imaging by optical coherence tomography included the posterior pole asymmetry analysis map. Data were analyzed with multiple linear regression models and correlation tests to examine the mean and variance of the measured thickness of the retina and its distribution relative to the presence and severity of KCN. RESULTS: A total of 24 subjects with keratoconus (48 eyes) and 14 normal subjects (28 eyes) enrolled in this study. The posterior pole retinal thickness, both superior and inferior hemifields, as well as the overall retinal thickness in KCN patients was greater than the control group. There was a direct correlation between the overall retinal thickness of the posterior pole and the severity of KCN (R2 = 0.422, P < 0.001). However, the variability of the retinal thickness showed no difference between KCN-afflicted and healthy eyes. CONCLUSION: Although KCN is a disease of the anterior segment of the eye, we found an orderly increase in posterior pole retinal thickness that is correlated with the severity of disease in KCN eyes compared to control. These findings suggest that the retina may maintain some degree of plasticity to respond to the degraded optical system of the eye.

Stigma, Discrimination, and Domestic Violence Experienced by Women Living with HIV: A Cross-sectional Study from Western India.

BACKGROUND: In India, social issues such as stigma and discrimination are still experienced by many women living with HIV (WLHIV) at various levels such as family, community, or health care settings even after a decline trend in HIV prevalence. OBJECTIVES: To assess stigma, discrimination, and domestic violence among WLHIV attending an antiretroviral therapy (ART) center and its association with unsafe sexual practices. MATERIALS AND METHODS: This cross-sectional study was carried out among WLHIV attending an ART center of a tertiary care hospital after obtaining approval from the institutional ethics committee. An interview schedule was used to collect data from WLHIV selected by systematic random sampling method on the day of interview. Data were collected after taking their written informed consent using a semistructured validated study instrument. Stigma and discrimination was assessed by a set of 7 and 11 closed-ended dichotomous-response questions, respectively. We measured self-reported occurrence of domestic violence and unsafe sexual practice. RESULTS: A total of 135 WLHIV were enrolled in this study. As high as 81% perceived stigma in their daily life while 41% reported to be discriminated. Domestic violence was experienced by 50.3% of the respondents. Majority of them (three-fourths) reported the type of violence to be physical as opposed to a quarter reporting sexual violence. Stigma, discrimination, and domestic violence were significantly associated with unsafe sexual practices. CONCLUSION: Social evils in the form of stigma, discrimination, and domestic violence are still faced by a remarkable proportion of WLHIV, and it has been found to be associated with unsafe sexual practices.

A Case Report Illustrating the Postoperative Course of Descemetorhexis without Endothelial Keratoplasty with Topical Netarsudil Therapy.

Fuchs endothelial corneal dystrophy (FECD) is the most common indication for corneal transplantation in the United States. Recently, descemetorhexis without endothelial keratoplasty (DWEK) or Descemet's stripping only (DSO) has become an attractive alternative to corneal transplantation for these patients. DSO circumvents the challenges associated with cadaveric donor corneal transplantation by tapping into the potential of the patient's own corneal endothelium to repair defects. Outcomes have been variable with emerging knowledge on predictive factors for success. Our case describes a 51-year-old patient with visually significant confluent central guttae from FECD who underwent a successful DSO with immediate post-operative use of the Rho-associated protein kinase (ROCK) inhibitor (netarsudil). We report the preoperative and post-operative slit lamp images, specular microscopy data, and corneal topography, thickness, and densitometry data. These represent a unique data set for this new surgical treatment option for FECD. Despite a small descemetorhexis, we show the improvement in corneal thickness and opacity extends beyond the boundaries of the descemetorhexis. Early initiation of a ROCK inhibitor was a successful treatment for this patient.

Influence of eyelid pigmentation on the diagnosis of meibomian gland dysfunction.

PURPOSE: To determine whether reliance on eyelid margin vascularization as a diagnostic criterion for meibomian gland dysfunction (MGD) results in underdiagnosis of MGD in individuals with dark skin pigmentation. PATIENTS AND METHODS: This cross-sectional study enrolled consecutive cornea clinic patients in Buffalo, New York. Eyelid margin vascularization was graded qualitatively from slit-lamp photos. Skin pigmentation was quantified from digital photos using red/green/blue (RGB) pixel analysis and dichotomized using the RGB median. MGD was defined as abnormal quantity or quality of meibum or increased pressure required to express meibum. Additional testing included infrared meibography, Schirmer's testing, and a dry eye questionnaire. Sensitivity of MGD diagnosis by visualization of vascularization, compared to diagnosis by expression of meibum, was estimated with and without stratification by skin pigmentation. RESULTS: Among 47 participants, 15-79 years old, meibomian gland truncation/dropout, abnormal tear production, and dry eye symptoms affected individuals of all skin pigmentations. Eyelid margin vascularization was less common in subjects with dark (n=21%) compared to light pigmentation (65%; p=0.002), although the prevalence of MGD assessed via clinical evaluation did not vary significantly between those groups. Use of eyelid margin vascularization alone was not sensitive (33%) for MGD diagnosis. The sensitivity was 17% when limited to those with dark pigmentation. CONCLUSION: Our findings highlight the importance of gland expression and suggest limiting reliance on eyelid margin vascularization for MGD diagnosis, especially in those with dark eyelid skin pigmentation.

A potent broadly neutralizing human RSV antibody targets conserved site IV of the fusion glycoprotein.

Respiratory syncytial virus (RSV) infection is the leading cause of hospitalization and infant mortality under six months of age worldwide; therefore, the prevention of RSV infection in all infants represents a significant unmet medical need. Here we report the isolation of a potent and broadly neutralizing RSV monoclonal antibody derived from a human memory B-cell. This antibody, RB1, is equipotent on RSV A and B subtypes, potently neutralizes a diverse panel of clinical isolates in vitro and demonstrates in vivo protection. It binds to a highly conserved epitope in antigenic site IV of the RSV fusion glycoprotein. RB1 is the parental antibody to MK-1654 which is currently in clinical development for the prevention of RSV infection in infants.