Immunogenicity, safety, and efficacy of the HPV vaccines among people living with HIV: A systematic review and meta-analysis

Background: Vaccines have been demonstrated to protect against high-risk human papillomavirus infection (HPV), including HPV-16/18, and cervical lesions among HIV negative women. However, their efficacy remains uncertain for people living with HIV (PLHIV).We systematically reviewed available evidence on HPV vaccine on immunological, virological, or other biological outcomes in PLHIV. Methods: We searched five electronic databases (PubMed, Medline and Embase, clinicaltrials.gov and the WHO clinical trial database) for longitudinal prospective studies reporting immunogenicity, virological, cytological, histological, clinical or safety endpoints following prophylactic HPV vaccination among PLHIV. We included studies published by February 11th, 2021. We summarized results, assessed study quality, and conducted meta-analysis and subgroup analyses, where possible. Findings: We identified 43 publications stemming from 18 independent studies (Ns =18), evaluating the quadrivalent (Ns =15), bivalent (Ns =4) and nonavalent (Ns =1) vaccines. A high proportion seroconverted for the HPV vaccine types. Pooled proportion seropositive by 28 weeks following 3 doses with the bivalent, quadrivalent, and nonavalent vaccines were 0.99 (95% confidence interval: 0.95-1.00, Ns =1), 0.99 (0.98-1.00, Ns =9), and 1.00 (0.99-1.00, Ns =1) for HPV-16 and 0.99 (0.96-1.00, Ns =1), 0.94 (0.91-0.96, Ns =9), and 1.00 (0.99-1.00, Ns =1) for HPV-18, respectively. Seropositivity remained high among people who received 3 doses despite some declines in antibody titers and lower seropositivity over time, especially for HPV-18, for the quadrivalent than the bivalent vaccine, and for HIV positive than negative individuals. Seropositivity for HPV-18 at 29-99 weeks among PLHIV was 0.72 (0.66-0.79, Ns =8) and 0.96 (0.92-0.99, Ns =2) after 3 doses of the quadrivalent and bivalent vaccine, respectively and 0.94 (0.90-0.98, Ns =3) among HIV-negative historical controls. Evidence suggests that the seropositivity after vaccination declines over time but it can lasts at least 2-4 years. The vaccines were deemed safe among PLHIV with few serious adverse events. Evidence of HPV vaccine efficacy against acquisition of HPV infection and/or associated disease from the eight trials available was inconclusive due to the low quality. Interpretation: PLHIV have a robust and safe immune response to HPV vaccination. Antibody titers and seropositivity rates decline over time but remain high. The lack of a formal correlate of protection and efficacy results preclude definitive conclusions on the clinical benefits. Nevertheless, given the burden of HPV disease in PLHIV, although the protection may be shorter or less robust against HPV-18, the robust immune response suggests that PLHIV may benefit from receiving HPV vaccination after acquiring HIV. Better quality studies are needed to demonstrate the clinical efficacy among PLHIV. Funding: World Health Organization. MRC Centre for Global Infectious Disease Analysis, Canadian Institutes of Health Research, UK Medical Research Council (MRC)

Heterogeneous mass distribution of the rubble-pile asteroid (101955) Bennu

The gravity field of a small body provides insight into its internal mass distribution. We used two approaches to measure the gravity field of the rubble-pile asteroid (101955) Bennu: (i) tracking and modeling the spacecraft in orbit about the asteroid and (ii) tracking and modeling pebble-sized particles naturally ejected from Bennu’s surface into sustained orbits. These approaches yield statistically consistent results up to degree and order 3, with the particle-based field being statistically significant up to degree and order 9. Comparisons with a constant-density shape model show that Bennu has a heterogeneous mass distribution. These deviations can be modeled with lower densities at Bennu’s equatorial bulge and center. The lower-density equator is consistent with recent migration and redistribution of material. The lower-density center is consistent with a past period of rapid rotation, either from a previous Yarkovsky-O’Keefe-Radzievskii-Paddack cycle or arising during Bennu’s accretion following the disruption of its parent body

Oseltamivir-Resistant Pandemic A/H1N1 Virus Is as Virulent as Its Wild-Type Counterpart in Mice and Ferrets

The neuraminidase inhibitor oseltamivir is currently used for treatment of patients infected with the pandemic A/H1N1 (pH1N1) influenza virus, although drug-resistant mutants can emerge rapidly and possibly be transmitted. We describe the characteristics of a pair of oseltamivir-resistant and oseltamivir-susceptible pH1N1 clinical isolates that differed by a single change (H274Y) in the neuraminidase protein. Viral fitness of pH1N1 isolates was assessed in vitro by determining replication kinetics in MDCK α2,6 cells and in vivo by performing experimental infections of BALB/c mice and ferrets. Despite slightly reduced propagation of the mutant isolate in vitro during the first 24 h, the wild-type (WT) and mutant resistant viruses induced similar maximum weight loss in mice and ferrets with an identical pyrexic response in ferrets (AUC of 233.9 and 233.2, P = 0.5156). Similarly, comparable titers were obtained for the WT and the mutant strains on days 1, 3, 6 and 9 post-infection in mouse lungs and on days 1–7 in ferret nasal washes. A more important perivascular (day 6) and pleural (days 6 and 12) inflammation was noted in the lungs of mice infected with the H274Y mutant, which correlated with increased pulmonary levels of IL-6 and KC. Such increased levels of IL-6 were also observed in lymph nodes of ferrets infected with the mutant strain. Furthermore, the H274Y mutant strain was transmitted to ferrets. In conclusion, viral fitness of the H274Y pH1N1 isolate is not substantially altered and has the potential to induce severe disease and to disseminate

Properties of Rubble-Pile Asteroid (101955) Bennu from OSIRIS-REx Imaging and Thermal Analysis

Establishing the abundance and physical properties of regolith and boulders on asteroids is crucial for understanding the formation and degradation mechanisms at work on their surfaces. Using images and thermal data from NASA's Origins, Spectral Interpretation, Resource Identification, and Security-Regolith Explorer (OSIRIS-REx) spacecraft, we show that asteroid (101955) Bennu's surface is globally rough, dense with boulders, and low in albedo. The number of boulders is surprising given Bennu's moderate thermal inertia, suggesting that simple models linking thermal inertia to particle size do not adequately capture the complexity relating these properties. At the same time, we find evidence for a wide range of particle sizes with distinct albedo characteristics. Our findings imply that ages of Bennu's surface particles span from the disruption of the asteroid's parent body (boulders) to recent in situ production (micrometre-scale particles)

The dynamic geophysical environment of (101955) Bennu based on OSIRIS-REx measurements

The top-shaped morphology characteristic of asteroid (101955) Bennu, often found among fast-spinning asteroids and binary asteroid primaries, may have contributed substantially to binary asteroid formation. Yet a detailed geophysical analysis of this morphology for a fast-spinning asteroid has not been possible prior to the Origins, Spectral Interpretation, Resource Identification, and Security-Regolith Explorer (OSIRIS-REx) mission. Combining the measured Bennu mass and shape obtained during the Preliminary Survey phase of the OSIRIS-REx mission, we find a notable transition in Bennu’s surface slopes within its rotational Roche lobe, defined as the region where material is energetically trapped to the surface. As the intersection of the rotational Roche lobe with Bennu’s surface has been most recently migrating towards its equator (given Bennu’s increasing spin rate), we infer that Bennu’s surface slopes have been changing across its surface within the last million years. We also find evidence for substantial density heterogeneity within this body, suggesting that its interior is a mixture of voids and boulders. The presence of such heterogeneity and Bennu’s top shape are consistent with spin-induced failure at some point in its past, although the manner of its failure cannot yet be determined. Future measurements by the OSIRIS-REx spacecraft will provide insight into and may resolve questions regarding the formation and evolution of Bennu’s top-shape morphology and its link to the formation of binary asteroids

Evidence for widespread hydrated minerals on asteroid (101955) Bennu

Early spectral data from the Origins, Spectral Interpretation, Resource Identification, and Security-Regolith Explorer (OSIRIS-REx) mission reveal evidence for abundant hydrated minerals on the surface of near-Earth asteroid (101955) Bennu in the form of a near-infrared absorption near 2.7 µm and thermal infrared spectral features that are most similar to those of aqueously altered CM-type carbonaceous chondrites. We observe these spectral features across the surface of Bennu, and there is no evidence of substantial rotational variability at the spatial scales of tens to hundreds of metres observed to date. In the visible and near-infrared (0.4 to 2.4 µm) Bennu’s spectrum appears featureless and with a blue (negative) slope, confirming previous ground-based observations. Bennu may represent a class of objects that could have brought volatiles and organic chemistry to Earth

Progression from latent infection to active disease in dynamic TB transmission models: a systematic review of the validity of modelling assumptions

Mathematical modelling is commonly used to evaluate infectious disease control policy, and is influential in shaping policy and budgets. Mathematical models necessarily make assumptions about disease natural history, and if these assumptions are not valid the results of these studies may be biased. We conducted a systematic review of published TB transmission models, to assess the validity of assumptions about progression to active disease following initial infection (PROSPERO ID CRD42016030009). We searched PubMed, Web of Science, Embase, Biosis, and Cochrane Library, and included studies from the earliest available date (1962) to August 31st 2017. We identified 312 studies that met inclusion criteria. Predicted TB incidence varied widely across studies for each risk factor investigated. For population groups with no individual risk factors, annual incidence varied by several orders of magnitude, and 20-year cumulative incidence ranged from close to 0% to 100%. A substantial fraction of modelled results were inconsistent with empirical evidence—for 10-year cumulative incidence 40% of modelled results were more than double or less than half the empirical estimates. These results demonstrate substantial disagreement between modelling studies on a central feature of TB natural history. Greater attention to reproducing known features of TB epidemiology would strengthen future TB modelling studies, and readers of modelling studies are recommended to assess how well those studies demonstrate their validity

Evaluation and classification of severity for 176 genes on an expanded carrier screening panel

BACKGROUND: Disease severity is important when considering genes for inclusion on reproductive expanded carrier screening (ECS) panels. We applied a validated and previously published algorithm that classifies diseases into four severity categories (mild, moderate, severe, and profound) to 176 genes screened by ECS. Disease traits defining severity categories in the algorithm were then mapped to four severity-related ECS panel design criteria cited by the American College of Obstetricians and Gynecologists (ACOG). METHODS: Eight genetic counselors (GCs) and four medical geneticists (MDs) applied the severity algorithm to subsets of 176 genes. MDs and GCs then determined by group consensus how each of these disease traits mapped to ACOG severity criteria, enabling determination of the number of ACOG severity criteria met by each gene. RESULTS: Upon consensus GC and MD application of the severity algorithm, 68 (39%) genes were classified as profound, 71 (40%) as severe, 36 (20%) as moderate, and one (1%) as mild. After mapping of disease traits to ACOG severity criteria, 170 out of 176 genes (96.6%) were found to meet at least one of the four criteria, 129 genes (73.3%) met at least two, 73 genes (41.5%) met at least three, and 17 genes (9.7%) met all four. CONCLUSION: This study classified the severity of a large set of Mendelian genes by collaborative clinical expert application of a trait-based algorithm. Further, it operationalized difficult to interpret ACOG severity criteria via mapping of disease traits, thereby promoting consistency of ACOG criteria interpretation