Vulnerable Sites Research Articles

A Novel Approach to Inhibit Intergranular Corrosion in Ferritic Stainless Steel Welds Using High-Speed Laser Cladding

Ferritic stainless steels are prone to localized corrosion phenomena such as pitting corrosion or intergranular corrosion, in particular when jointed by fusion welding processes. State-of-the-art techniques to avoid intergranular corrosion mainly consist of alternating alloy concepts or post-weld heat-treatments—all of which are associated with increased production costs. Hence, the present investigation seeks to introduce a novel approach for the inhibition of intergranular corrosion in ferritic stainless steel welds through the use of high-speed laser cladding. Here, vulnerable sites prone to intergranular corrosion along the weld seam area are coated with a chemically resistant alloy, whereby an overlap is achieved. Optical and electron microscopy as well as computer tomography and tensile tests reveal that the detrimental effects of intergranular corrosion in both stabilized and unstabilized ferritic stainless steel are substantially reduced. In addition to that, the effects of varying overlap widths on the identified corrosion phenomena are studied. Moreover, the resulting dilution and precipiation phenomena at the clad–sheet interface are thoroughly characterized by electron backscatter diffraction and energy dispersive X-ray spectroscopy, whereby interrelationships to corrosion resistance can be drawn. As a result of this investigation, the number of techniques for the inhibition of intergranular corrosion is enlarged, and substantial cost-saving potentials in the manufacturing industry are unlocked.

Assessment of bank erosion and its impact on land use and land cover dynamics of Mahananda River basin (Upper) in the Sub-Himalayan North Bengal, India

Bank erosion is the predominant character of River Mahananda in the Sub-Himalayan North Bengal. The present study aims to identify the bank erosion mechanism as well as the impact of river bank erosion on land use and land cover (LULC) dynamics of the study area. Survey of India (SOI) topographical map 78 B/5 (1975) and satellite imageries for the temporal year of 1991 and 2019 from USGS have been used for the study. For the assessment of bank erosion process Bank erosion hazard index (BEHI) model has been adopted here. The channel migration has been delineated by the superimposition of temporal bank lines extracted from the temporal satellite imageries. LULC analysis has been carried out through the supervised classification technique using remote sensing and GIS tools. Form the assessment of BEHI it can be visualized that the scores have been ranging from 30.75 to 44.30 which indicates high to very high vulnerable areas under fluvial erosion. The channel migration for the temporal period from 1991 to 2019 is ranging from 7.72 to 411.16 m along the studied reach which reflects the high erosion effectiveness. From LULC classes it has been assessed that settled or built-up areas have been increased and the water body is gradually decreased overall in the study area. The study resulted that the river bank erosion has its direct impact on land use of the studied area. In the study vulnerable sites to fluvial erosion have been delineated and unplanned land use can be managed through sustainable way.

Investigation of the Fatigue Stress of Orthotropic Steel Decks Based on an Arch Bridge with the Application of the Arlequin Method.

Orthotropic steel decks are widely used in the construction of steel bridges. Although there are many fatigue-evaluation methods stipulated by codes, unexpected fatigue cracks are still detected in some bridges. To justify whether the local finite element model commonly used in fatigue investigations on orthotropic decks can correctly instruct engineering practices, the Arlequin framework is applied in this paper to determine the full fatigue stress under traffic loads. The convergence on and validity of this application for orthotropic decks are checked. Results show that the Arlequin model for deck-fatigue analysis established in this paper tends to be an efficient method for complete fatigue stress acquisition, whereby the vulnerable sites of orthotropic steel decks under traffic loads are defined. Vehicles near the flexible components, such as hangers or cables, can have adverse effects on the fatigue durability of decks. Additionally, the total number of vehicles and their arrangement concentration also affect fatigue performance. Complex traffic conditions cannot be fully loaded in local models. Regardless of the gross bridge mechanics and deck deformation, the fatigue stress range is underestimated by about 30–40%. Such a difference in fatigue assessment seems to explain the premature cracks observed in orthotropic steel decks.

Diversity and distribution of lichens from the Cerro Duida and adjacent areas, Alto Orinoco, Amazonas, Venezuela

Increasing temperature and changing land-use in the Guayana Shield and Amazonia result in an accelerated decline of sensitive lichen populations. Monitoring of these populations by biological plot inventories in particularly vulnerable sites is urgently needed. In order to know the diversity and distribution of lichen species at the Alto Orinoco, Parque Nacional Duida-Marahuaca and nearby areas from Amazonas state, Venezuela, lichens were sampled during four expeditions in more than 40 plots located from 200 m (premontane forest) to more than 1500 m elevation (altotepuyana vegetation). Additional data were obtained from literature and herbaria. Our assessment, although incomplete, revealed 205 described species, 150 undescribed species, 84 genera and 27 families. Among the described species 162 were observed in the basimontane vegetation, 38 in the montane vegetation, 24 in the altotepuyana vegetation, while 20 appear to be endemic to the study area. Sixty-nine species are new records for the Cerro Duida. A checklist with taxonomic and ecological data is presented. Five new species and one new variety are described: Cladonia duidana V.Marcano & A.Morales sp. nov. (Cladoniaceae), Pertusaria orinoquensis V.Marcano sp. nov., Sticta kunuhana V.Marcano sp. nov. (Lobariaceae), S. spruceana V.Marcano sp. nov. (Lobariaceae), Xanthoparmelia esmeraldensis V.Marcano & A.Morales sp. nov. (Parmeliaceae), and Lepraria arbuscula (Nyl.) Lendemer & Hodk. var. fumarprotocetrarica V.Marcano var. nov.

Post-Industrial sites and the clash of narratives: The case of the Gdańsk shipyard

This article explores the clash of various narratives around the Gdańsk shipyard, one of the famous examples of a post-industrial heritage site with a significant political past, located in Poland. The analysis is placed within the larger context of contemporary debates on heritage and the specificity of post-industrial sites, showing how vulnerable and fragile foundations such sites may have, as well as how they are susceptible to various manipulations. This study explores the process of construction of heritage sites and their contradictory narratives by referring to one particular aspect of the Polish past and its institutional representation in the form of post-industrial heritage. First, it refers to the contemporary idea of heritage and briefly explains the relation between heritage and memory. It also describes the role of heritage in the tourism industry emphasizing various expectations and demands that are made for memory sites. Then it analyses the idea and specificity of post-industrial heritage as well as the paradox of its universality. Finally, it refers to the Gdańsk shipyard as an example of post-industrial heritage space which serves various demands and visions that reflect a multiplicity of narratives. Keywords: heritage sites, post-industrial, narrative, Poland, Gdańsk shipyard

Lunapark-dependent formation of a virus-induced ER exit site contains multi-tubular ER junctions that promote viral ER-to-cytosol escape.

Viruses rearrange host membranes to support different entry steps. Polyomavirus simian virus 40 (SV40) reorganizes the endoplasmic reticulum (ER) membrane to generate focus structures that enable virus ER-to-cytosol escape, a decisive infection step. The molecular architecture of the ER exit site that might illuminate why it is ideally suited for membrane penetration is unknown. Here 3D focused ion beam scanning electron microscopy (FIB-SEM) reconstruction reveals that the ER focus structure consists of multi-tubular ER junctions where SV40 preferentially localizes, suggesting that tubular branch points are virus ER-to-cytosol penetration sites. Functional analysis demonstrates that lunapark-an ER membrane protein that typically stabilizes three-way ER junctions-relocates to the ER foci, where it supports focus formation, leading to SV40 ER escape and infection. Our results reveal how a virus repurposes the activity of an ER membrane protein to form a virus-induced ER substructure required for membrane escape and suggest that ER tubular junctions are vulnerable sites exploited by viruses for membrane penetration.

GIS-based multi-criteria modelling of flood risk susceptibility in Port Louis, Mauritius: Towards resilient flood management

Economic growth and population expansion in Mauritius have driven unprecedented rates of development. Most notably, increased urbanization of flood-prone regions has exacerbated challenges around resilience and vulnerability to recurrent flooding. We implement a multi-criteria model consisting of a physical-oriented, a social-oriented and an economic-oriented scenario to identify highly vulnerable sites to flooding in the capital city, Port Louis. Social, technical, economic and legal perspectives are incorporated to propose comprehensive flood management strategies. The aim is to minimize the physical impacts of floods while also addressing the broader social and economic risks. Location-based flood management strategies are thereafter proposed to increase the resilience of the city to flooding. Measures include, inter alia, the construction of an underground stormwater storage tank at Champ de Mars, establishment of flood refugee camps at Vallée Pitot and Cité La Cure, reviewing building regulations and urban planning, replacement of the Caudan Underpass by an Overhead Bridge, green renaturing of rivers in downstream areas, construction of a retention pond on the downhill slope of the mountain at Bell Village, and the setting up of a diversion tunnel linking St Louis River to Grand River North West. The approach adopted will allow an understanding of the geography of flooding in Port Louis and support management decisions for limiting its impacts.

Uncovering a conserved vulnerability site in SARS‐CoV‐2 by a human antibody

An essential step for SARS‐CoV‐2 infection is the attachment to the host cell receptor by its Spike receptor‐binding domain (RBD). Most of the existing RBD‐targeting neutralizing antibodies block the receptor‐binding motif (RBM), a mutable region with the potential to generate neutralization escape mutants. Here, we isolated and structurally characterized a non‐RBM‐targeting monoclonal antibody (FD20) from convalescent patients. FD20 engages the RBD at an epitope distal to the RBM with a KD of 5.6 nM, neutralizes SARS‐CoV‐2 including the current Variants of Concern such as B.1.1.7, B.1.351, P.1, and B.1.617.2 (Delta), displays modest cross‐reactivity against SARS‐CoV, and reduces viral replication in hamsters. The epitope coincides with a predicted “ideal” vulnerability site with high functional and structural constraints. Mutation of the residues of the conserved epitope variably affects FD20‐binding but confers little or no resistance to neutralization. Finally, in vitro mode‐of‐action characterization and negative‐stain electron microscopy suggest a neutralization mechanism by which FD20 destructs the Spike. Our results reveal a conserved vulnerability site in the SARS‐CoV‐2 Spike for the development of potential antiviral drugs.

A potent and protective human neutralizing antibody targeting a novel vulnerable site of Epstein-Barr virus

Epstein-Barr virus (EBV) is associated with a range of epithelial and B cell malignancies as well as autoimmune disorders, for which there are still no specific treatments or effective vaccines. Here, we isolate EBV gH/gL-specific antibodies from an EBV-infected individual. One antibody, 1D8, efficiently neutralizes EBV infection of two major target cell types, B cells and epithelial cells. In humanized mice, 1D8 provides protection against a high-dose EBV challenge by substantially reducing viral loads and associated tumor burden. Crystal structure analysis reveals that 1D8 binds to a key vulnerable interface between the D-I/D-II domains of the viral gH/gL protein, especially the D-II of the gH, thereby interfering with the gH/gL-mediated membrane fusion and binding to target cells. Overall, we identify a potent and protective neutralizing antibody capable of reducing the EBV load. The novel vulnerable site represents an attractive target that is potentially important for antibody and vaccine intervention against EBV infection.

Setting priorities for climate change adaptation of Critical Sites in the Africa-Eurasian waterbird flyways.

Despite their importance for biodiversity and ecosystem services, wetlands are among the most threatened ecosystems globally. The conservation of many migratory waterbirds depends on the conservation of a network of key sites along their flyways. However, the suitability of these sites is changing under climate change, and it is important that management of individual sites in the network adapts to these changes. Using bioclimatic models that also account for changes in inundation, we found that projected climate change will reduce habitat suitability for waterbirds at 57.5% of existing Critical Sites within Africa‐Eurasia, varying from 20.1% in Eastern Europe to 87.0% in Africa. African and Middle East sites are particularly threatened, comprising 71 of the 100 most vulnerable sites. By highlighting priority sites for conservation and classifying Critical Sites into Climate Change Adaptation Strategy (CCAS) classes, our results can be used to support the climate change adaptation of both individual sites and the entire site network.

A site of vulnerability at V3 crown defined by HIV-1 bNAb M4008_N1

Identification of vulnerable sites defined by broadly neutralizing antibodies (bNAbs) on HIV-1 envelope (Env) is crucial for vaccine design, and we present here a vulnerable site defined by bNAb M4008_N1, which neutralizes about 40% of a tier-2 virus panel. A 3.2 Å resolution cryo-EM structure of M4008_N1 in complex with BG505 DS-SOSIP reveals a large, shallow protein epitope surface centered at the V3 crown of gp120 and surrounded by key glycans. M4008_N1 interacts with gp120 primarily through its hammerhead CDR H3 to form a β-sheet interaction with the V3 crown hairpin. This makes M4008_N1 compatible with the closed conformation of the prefusion Env trimer, and thus distinct from other known V3 crown mAbs. This mode of bNAb approaching the immunogenic V3 crown in the native Env trimer suggests a strategy for immunogen design targeting this site of vulnerability.

Perceptions of climate change and adaptation: A subarctic archipelago perspective (Saint-Pierre-and-Miquelon, North America)

Climate change is projected to challenge adaptation capacity in small islands worldwide due to rising temperatures, sea-level rise, extreme events and changing rainfall patterns. However, adaptation planning and implementation may be delayed where people perceive a lack of urgency and put forward competing priorities such as economic development. Here, we assess perceptions of climate change and adaptation in Saint-Pierre-and-Miquelon, a subarctic archipelago located south of Newfoundland, Canada. We performed and analysed a social survey reaching 289 individuals out of a population of 6260, through a questionnaire conducted both face-to-face and online. We show that inhabitants of Saint-Pierre-and-Miquelon generally have a clear understanding of climate change and perceive adaptation as urgent for a number of vulnerable coastal sites. Despite some disagreements on adaptation options and the timing for implementation, it is noteworthy that even relocation action is mentioned and sometimes requested. We show that perceptions of climate change and of adaptation within Saint-Pierre-and-Miquelon are heavily influenced by place attachment, personal experience of coastal hazards and environmental awareness. From a methodological point of view, our results highlight the relevance of using online surveys in well-connected but geographically isolated communities. From an adaptation perspective, our results suggest that people's perceptions and beliefs are not only a barrier, but rather offer in some cases opportunities for adaptation planning and implementation. Such favourable attitudes toward adaptation do not exist across all small islands, so our results may be useful in determining the conditions under which people's perceptions are conducive to adaptation.

Present vs. Future Property Losses From a 100-Year Coastal Flood: A Case Study of Grand Isle, Louisiana

Louisiana, U.S.A., is among the world's most vulnerable places to coastal flooding. Increasing frequency/intensity of natural hazards under climate change scenarios is expected to exacerbate Louisiana's coastal flood risk. Although many factors are involved, land subsidence from marshland compaction and underground resource extraction, shoreline erosion accelerated by eustatic sea level rise (ESLR), and tropical-cyclone-induced storm surge are among the most important. While past research has focused on flood risk assessment and mitigation strategies, including climate change scenarios, few studies examine all of these factors collectively. This study shows present pluvial flood depth and the contributions of additional coastal subsidence and ESLR toward future (2050) pluvial flooding. Then, current tropical-storm-induced storm surge and future storm surge depth modeled by Louisiana's Coastal Protection and Restoration Authority (CPRA) under climate change scenarios are presented. Present and future 100-year pluvial flood and storm surge losses (separately, 2020$) to structures and their contents are estimated at the individual building level for Grand Isle, Louisiana, a barrier island town of ecological, economic, historical, recreational, cultural, and aesthetic treasure. Results suggest that the average 100-year pluvial flood depth in buildings will increase by 1.35 feet by 2050, with subsidence contributing over 82% of this total. Subsidence is projected to escalate structure and content losses by ~17% above losses in 2017, while ESLR may contribute ~3% above 2017 losses. A 100-year tropical-cyclone-induced storm surge event amid a “low” scenario of environmental change as defined by CPRA would increase Grand Isle's structure and content losses by 68–74% above the 2017 value by 2027, 141–149% by 2042, and 346–359% by 2067. The (“high”) scenario of environmental change would increase the 100-year storm surge losses by 85–91% above the 2017 value by 2027, 199–218% by 2042, and 407–415% by 2067. Outcomes from this study will offer a more realistic risk assessment model and will direct flood risk managers, property owners, and other stakeholders to build a comprehensive framework to minimize future flood risk in one of the most vulnerable sites in the U.S.A. to coastal flooding.

Structure-guided envelope trimer design in HIV-1 vaccine development: a narrative review.

IntroductionThe development of a human immunodeficiency virus 1 (HIV‐1) vaccine remains a formidable challenge. An effective vaccine likely requires the induction of broadly neutralizing antibodies (bNAbs), which likely involves the use of native‐like HIV‐1 envelope (Env) trimers at some or all stages of vaccination. Development of such trimers has been very difficult, but much progress has been made in the past decade, starting with the BG505 SOSIP trimer, elucidation of its atomic structure and implementing subsequent design iterations. This progress facilitated understanding the weaknesses of the Env trimer, fuelled structure‐guided HIV‐1 vaccine design and assisted in the development of new vaccine designs. This review summarizes the relevant literature focusing on studies using structural biology to reveal and define HIV‐1 Env sites of vulnerability; to improve Env trimers, by creating more stable versions; understanding antibody responses in preclinical vaccination studies at the atomic level; understanding the glycan shield; and to improve “on‐target” antibody responses versus “off‐target” responses.MethodsThe authors conducted a narrative review of recently published articles that made a major contribution to HIV‐1 structural biology and vaccine design efforts between the years 2000 and 2021.DiscussionThe field of structural biology is evolving at an unprecedented pace, where cryo‐electron microscopy (cryo‐EM) and X‐ray crystallography provide complementary information. Resolving protein structures is necessary for defining which Env surfaces are accessible for the immune system and can be targeted by neutralizing antibodies. Recently developed techniques, such as electron microscopy‐based polyclonal epitope mapping (EMPEM) are revolutionizing the way we are analysing immune responses and shed light on the immunodominant targets on new vaccine immunogens. Such information accelerates iterative vaccine design; for example, by reducing undesirable off‐target responses, while improving immunogens to drive the more desirable on‐target responses.ConclusionsResolving high‐resolution structures of the HIV‐1 Env trimer was instrumental in understanding and improving recombinant HIV‐1 Env trimers that mimic the structure of viral HIV‐1 Env spikes. Newly emerging techniques in structural biology are aiding vaccine design efforts and improving immunogens. The role of structural biology in HIV‐1 vaccine design has indeed become very prominent and is unlikely to diminish any time soon.

Low-dose in vivo protection and neutralization across SARS-CoV-2 variants by monoclonal antibody combinations

Prevention of viral escape and increased coverage against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern require therapeutic monoclonal antibodies (mAbs) targeting multiple sites of vulnerability on the coronavirus spike glycoprotein. Here we identify several potent neutralizing antibodies directed against either the N-terminal domain (NTD) or the receptor-binding domain (RBD) of the spike protein. Administered in combinations, these mAbs provided low-dose protection against SARS-CoV-2 infection in the K18-human angiotensin-converting enzyme 2 mouse model, using both neutralization and Fc effector antibody functions. The RBD mAb WRAIR-2125, which targets residue F486 through a unique heavy-chain and light-chain pairing, demonstrated potent neutralizing activity against all major SARS-CoV-2 variants of concern. In combination with NTD and other RBD mAbs, WRAIR-2125 also prevented viral escape. These data demonstrate that NTD/RBD mAb combinations confer potent protection, likely leveraging complementary mechanisms of viral inactivation and clearance.

Immunizations with diverse sarbecovirus receptor-binding domains elicit SARS-CoV-2 neutralizing antibodies against a conserved site of vulnerability

Viral mutations are an emerging concern in reducing SARS-CoV-2 vaccination efficacy. Second-generation vaccines will need to elicit neutralizing antibodies against sites that are evolutionarily conserved across the sarbecovirus subgenus. Here, we immunized mice containing a human antibody repertoire with diverse sarbecovirus receptor-binding domains (RBDs) to identify antibodies targeting conserved sites of vulnerability. Antibodies with broad reactivity against diverse clade B RBDs targeting the conserved class 4 epitope, with recurring IGHV/IGKV pairs, were readily elicited but were non-neutralizing. However, rare class 4 antibodies binding this conserved RBD supersite showed potent neutralization of SARS-CoV-2 and all variants of concern. Structural analysis revealed that the neutralizing ability of cross-reactive antibodies was reserved only for those with an elongated CDRH3 that extends the antiparallel beta-sheet RBD core and orients the antibody light chain to obstruct ACE2-RBD interactions. These results identify a structurally defined pathway for vaccine strategies eliciting escape-resistant SARS-CoV-2 neutralizing antibodies.

Neutralizing antibody 5-7 defines a distinct site of vulnerability in SARS-CoV-2 spike N-terminal domain.

Antibodies that potently neutralize SARS-CoV-2 target mainly the receptor-binding domain or the N-terminal domain (NTD). Over a dozen potently neutralizing NTD-directed antibodies have been studied structurally, and all target a single antigenic supersite in NTD (site 1). Here, we report the cryo-EM structure of a potent NTD-directed neutralizing antibody 5-7, which recognizes a site distinct from other potently neutralizing antibodies, inserting a binding loop into an exposed hydrophobic pocket between the two sheets of the NTD β sandwich. Interestingly, this pocket was previously identified as the binding site for hydrophobic molecules, including heme metabolites, but we observe that their presence does not substantially impede 5-7 recognition. Mirroring its distinctive binding, antibody 5-7 retains neutralization potency with many variants of concern (VOCs). Overall, we reveal that a hydrophobic pocket in NTD proposed for immune evasion can be used by the immune system for recognition.

Two Distinct Lysosomal Targeting Strategies Afford Trojan Horse Antibodies With Pan-Filovirus Activity.

Multiple agents in the family Filoviridae (filoviruses) are associated with sporadic human outbreaks of highly lethal disease, while others, including several recently identified agents, possess strong zoonotic potential. Although viral glycoprotein (GP)-specific monoclonal antibodies have demonstrated therapeutic utility against filovirus disease, currently FDA-approved molecules lack antiviral breadth. The development of broadly neutralizing antibodies has been challenged by the high sequence divergence among filovirus GPs and the complex GP proteolytic cleavage cascade that accompanies filovirus entry. Despite this variability in the antigenic surface of GP, all filoviruses share a site of vulnerability—the binding site for the universal filovirus entry receptor, Niemann-Pick C1 (NPC1). Unfortunately, this site is shielded in extracellular GP and only uncovered by proteolytic cleavage by host proteases in late endosomes and lysosomes, which are generally inaccessible to antibodies. To overcome this obstacle, we previously developed a ‘Trojan horse’ therapeutic approach in which engineered bispecific antibodies (bsAbs) coopt viral particles to deliver GP:NPC1 interaction-blocking antibodies to their endo/lysosomal sites of action. This approach afforded broad protection against members of the genus Ebolavirus but could not neutralize more divergent filoviruses. Here, we describe next-generation Trojan horse bsAbs that target the endo/lysosomal GP:NPC1 interface with pan-filovirus breadth by exploiting the conserved and widely expressed host cation-independent mannose-6-phosphate receptor for intracellular delivery. Our work highlights a new avenue for the development of single therapeutics protecting against all known and newly emerging filoviruses.

Grooming site preferences in black capuchin monkeys: Hygienic vs. social functions revisited.

When primates groom each other, they tend to concentrate on those parts of the body they cannot efficiently self-groom (i.e., not visually accessible), and prefer to intensify grooming in areas with high hair density, thus suggesting a hygienic function. However, preferences for some body sites over others during social grooming may also result from different degrees of social bonding and relative dominance. To assess the relative importance of physical (hygienic) and social factors, we examined grooming interactions in two groups of wild black capuchin monkeys (Sapajus nigritus) during 15 nonconsecutive months. We evaluated the distribution of social grooming across body sites according to their accessibility by self-grooming and hair density. At the same time, we assessed whether the degree of dyadic social bonding affects the relative body orientation between groomer and groomee and the access to vulnerable body sites (e.g., face, throat, groin) during grooming. As expected, capuchins preferentially groomed inaccessible body sites (e.g., back and head), with a disproportionate effort directed to the tufts of their partners. We found that dyadic social bond strength, together with rank distance, significantly affected the proportion of grooming in ventro-ventral body relative orientation only in dominant-subordinate groomer-groomee dyads. This may indicate that, when two individuals differ in rank but are strongly bonded, the level of uncertainty related to the social context is already resolved and thus grooming per se is no longer perceived by the subordinate as an uncertain/risky situation. We found no effect of social bonding on grooming vulnerable body sites for any type of dyad. Our findings suggest that grooming site preferences in black capuchin monkeys simultaneously reflect hygienic and social functions.

A Structural Update of Neutralizing Epitopes on the HIV Envelope, a Moving Target.

Antibodies that can neutralize diverse HIV-1 strains develop in ~10–20% of HIV-1 infected individuals, and their elicitation is a goal of vaccine design. Such antibodies can also serve as therapeutics for those who have already been infected with the virus. Structural characterizations of broadly reactive antibodies in complex with the HIV-1 spike indicate that there are a limited number of sites of vulnerability on the spike. Analysis of their structures can help reveal commonalities that would be useful in vaccine design and provide insights on combinations of antibodies that can be used to minimize the incidence of viral resistance mutations. In this review, we give an update on recent structures determined of the spike in complex with broadly neutralizing antibodies in the context of all epitopes on the HIV-1 spike identified to date.