• Anti-SARS-CoV-2 immune responses in patients receiving an allogeneic stem cell or organ transplant

      Atanackovic, Djordje; Luetkens, Tim; Avila, Stephanie V.; Hardy, Nancy M.; Lutfi, Forat; Sanchez-Petitto, Gabriela; Mause, Erica Vander; Glynn, Nicole; Mannuel, Heather D.; Alkhaldi, Hanan; et al. (MDPI AG, 2021-07-03)
      Patients after autologous (autoSCT) and allogeneic stem cell transplantation (alloSCT) are at an increased risk of COVID-19-related morbidity and mortality, compounded by an immune system weakened by the underlying malignancy and prior treatments. Allogeneic transplantation, including stem cell and solid organ transplants, requires intensive immunosuppressive prophylaxis, which may further undermine the development of a protective vaccine-induced anti-viral immunity. Herein, we report on short- and long-term antiviral immune responses in two peri-stem cell transplant recipients and a third patient who received a COVID-19 vaccination after kidney transplantation. Our data indicate that: (1) patients post-alloSCT may be able to mount an anti-COVID-19 immune response; however, a sufficient time interval between transplant and exposure may be of critical importance; (2) alloSCT recipients with preexisting anti-SARS-CoV-2 immunity are at risk for losing protective humoral immunity following transplantation, particularly if the stem-cell donor lacks antiviral immunity, e.g., vaccine-derived immunity; and (3) some post-transplant patients are completely unable to build an immune response to a COVID-19 vaccine, perhaps based on the prophylactic suppression of T cell immunity.
    • Building momentum for malaria vaccine research and development: key considerations

      Chitnis, Chetan E; Schellenberg, David; Vekemans, Johan; Asturias, Edwin J; Bejon, Philip; Collins, Katharine A; Crabb, Brendan S; Herrera, Socrates; Laufer, Miriam; Rabinovich, N Regina; et al. (Springer Nature, 2020-11-23)
      To maintain momentum towards improved malaria control and elimination, a vaccine would be a key addition to the intervention toolkit. Two approaches are recommended: (1) promote the development and short to medium term deployment of first generation vaccine candidates and (2) support innovation and discovery to identify and develop highly effective, long-lasting and affordable next generation malaria vaccines.
    • Clinical endpoints for efficacy studies

      Porter, Chad K.; Gutierrez, Ramiro L.; Kotloff, Karen L. (Elsevier Ltd., 2019-01-01)
      Well-established, validated and clinically meaningful primary and secondary endpoints are critical inadvancing vaccines through proof of principal studies, licensure and pre-qualification. To that end, the field of vaccine development for Shigella, enterotoxigenic Escherichia coli (ETEC) as well as other enteric pathogens would benefit greatly from a focused review of clinical endpoints and the use of common end-points across the field to enable study-to-study comparisons as well as comparative assessments between vaccine candidates. A workshop was conducted to review clinical endpoints from controlled human challenge studies, field studies in naïve adult travelers and pediatric studies in low-middle income countries and to develop a consensus on clinical endpoints for future vaccine trials. Following sequential presentations on different study designs (CHIM, travelers’ efficacy and pediatric efficacy), workshop participants broke into three simultaneous workgroups focused on those study designs to discuss a number of topics key to clinical endpoints specific to each study design. Previously utilized endpoints were reviewed with an eye towards potentially novel endpoints for future studies and consideration of the disease parameters and spectrum of disease targeted for prevention. The strength of support among workshop participants for the use of various endpoints is summarized as are recommendations for additional endpoints to be considered in future studies. It is anticipated that this report will facilitate endpoint determination in future efficacy trials of vaccine candidates.
    • Cost-effectiveness of infant respiratory syncytial virus preventive interventions in Mali: A modeling study to inform policy and investment decisions

      Laufer, Rachel S; Driscoll, Amanda J; Baral, Ranju; Buchwald, Andrea G; Campbell, James D; Coulibaly, Flanon; Diallo, Fatoumata; Doumbia, Moussa; Galvani, Alison P; Haidara, Fadima C; et al. (Elsevier Ltd., 2021-07-26)
      Importance: Low- and middle-income countries have a high burden of respiratory syncytial virus lower respiratory tract infections. A monoclonal antibody administered monthly is licensed to prevent these infections, but it is cost-prohibitive for most low- and middle-income countries. Long-acting monoclonal antibodies and maternal vaccines against respiratory syncytial virus are under development. Objective: We estimated the likelihood of respiratory syncytial virus preventive interventions (current monoclonal antibody, long-acting monoclonal antibody, and maternal vaccine) being cost-effective in Mali. Design: We modeled age-specific and season-specific risks of respiratory syncytial virus lower respiratory tract infections within monthly cohorts of infants from birth to six months. We parameterized with respiratory syncytial virus data from Malian cohort studies, as well as product efficacy from clinical trials. Integrating parameter uncertainty, we simulated health and economic outcomes for status quo without prevention, intra-seasonal monthly administration of licensed monoclonal antibody, pre-seasonal birth dose administration of a long-acting monoclonal antibody, and maternal vaccination. We then calculated the incremental cost-effectiveness ratio of each intervention compared to status quo from the perspectives of the government, donor, and society. Results: At a price of $3 per dose and from the societal perspective, current monoclonal antibody, long-acting monoclonal antibody, and maternal vaccine would have incremental cost-effectiveness ratios of $4280 (95% CI $1892 to $122,434), $1656 (95% CI $734 to $9091), and $8020 (95% CI $3501 to $47,047) per disability-adjusted life-year averted, respectively. Conclusions and Relevance: In Mali, long-acting monoclonal antibody is likely to be cost-effective from both the government and donor perspectives at $3 per dose. Maternal vaccine would need higher efficacy over that measured by a recent trial in order to be considered cost-effective. © 2021 The Authors
    • COVID-19 preparedness: capacity to manufacture vaccines, therapeutics and diagnostics in sub-Saharan Africa

      Bright, B.; Babalola, C.P.; Sam-Agudu, N.A.; Onyeaghala, A.A.; Olatunji, A.; Aduh, U.; Sobande, P.O.; Crowell, T.A.; Tebeje, Y.K.; Phillip, S.; et al. (Springer Nature, 2021-03-03)
      Objective: The COVID-19 pandemic is a biosecurity threat, and many resource-rich countries are stockpiling and/or making plans to secure supplies of vaccine, therapeutics, and diagnostics for their citizens. We review the products that are being investigated for the prevention, diagnosis, and treatment of COVID-19; discuss the challenges that countries in sub-Saharan Africa may face with access to COVID-19 vaccine, therapeutics, and diagnostics due to the limited capacity to manufacture them in Africa; and make recommendations on actions to mitigate these challenges and ensure health security in sub-Saharan Africa during this unprecedented pandemic and future public-health crises. Main body: Sub-Saharan Africa will not be self-reliant for COVID-19 vaccines when they are developed. It can, however, take advantage of existing initiatives aimed at supporting COVID-19 vaccine access to resource-limited settings such as partnership with AstraZeneca, the Coalition for Epidemic Preparedness and Innovation, the Global Alliance for Vaccine and Immunisation, the Serum Institute of India, and the World Health Organization's COVID-19 Technology Access Pool. Accessing effective COVID-19 therapeutics will also be a major challenge for countries in sub-Saharan Africa, as production of therapeutics is frequently geared towards profitable Western markets and is ill-adapted to sub-Saharan Africa realities. The region can benefit from pooled procurement of COVID-19 therapy by the Africa Centres for Disease Control and Prevention in partnership with the African Union. If the use of convalescent plasma for the treatment of patients who are severely ill is found to be effective, access to the product will be minimally challenging since the region has a pool of recovered patients and human resources that can man supportive laboratories. The region also needs to drive the local development of rapid-test kits and other diagnostics for COVID-19. Conclusion: Access to vaccines, therapeutics, and diagnostics for COVID-19 will be a challenge for sub-Saharan Africans. This challenge should be confronted by collaborating with vaccine developers; pooled procurement of COVID-19 therapeutics; and local development of testing and diagnostic materials. The COVID-19 pandemic should be a wake-up call for sub-Saharan Africa to build vaccines, therapeutics, and diagnostics manufacturing capacity as one of the resources needed to address public-health crises. Copyright 2021, The Author(s).
    • Diverse antiviral IgG effector activities are predicted by unique biophysical antibody features

      Cheng, Hao D; Dowell, Karen G; Bailey-Kellogg, Chris; Goods, Brittany A; Love, J Christopher; Ferrari, Guido; Alter, Galit; Gach, Johannes; Forthal, Donald N; Lewis, George K; et al. (Springer Nature, 2021-10-30)
      Background: The critical role of antibody Fc-mediated effector functions in immune defense has been widely reported in various viral infections. These effector functions confer cellular responses through engagement with innate immune cells. The precise mechanism(s) by which immunoglobulin G (IgG) Fc domain and cognate receptors may afford protection are poorly understood, however, in the context of HIV/SHIV infections. Many different in vitro assays have been developed and utilized to measure effector functions, but the extent to which these assays capture distinct antibody activities has not been fully elucidated. Results: In this study, six Fc-mediated effector function assays and two biophysical antibody profiling assays were performed on a common set of samples from HIV-1 infected and vaccinated subjects. Biophysical antibody profiles supported robust prediction of diverse IgG effector functions across distinct Fc-mediated effector function assays. While a number of assays showed correlated activities, supervised machine learning models indicated unique antibody features as primary contributing factors to the associated effector functions. Additional experiments established the mechanistic relevance of relationships discovered using this unbiased approach. Conclusions: In sum, this study provides better resolution on the diversity and complexity of effector function assays, offering a clearer perspective into this family of antibody mechanisms of action to inform future HIV-1 treatment and vaccination strategies.
    • Does respiratory syncytial virus lower respiratory illness in early life cause recurrent wheeze of early childhood and asthma? Critical review of the evidence and guidance for future studies from a World Health Organization-sponsored meeting

      Driscoll, A.J.; Arshad, S.H.; Bont, L. (Elsevier Ltd, 2020)
      Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection (LRTI) and hospitalization in infants and children globally. Many observational studies have found an association between RSV LRTI in early life and subsequent respiratory morbidity, including recurrent wheeze of early childhood (RWEC) and asthma. Conversely, two randomized placebo-controlled trials of efficacious anti-RSV monoclonal antibodies (mAbs) in heterogenous infant populations found no difference in physician-diagnosed RWEC or asthma by treatment group. If a causal association exists and RSV vaccines and mAbs can prevent a substantial fraction of RWEC/asthma, the full public health value of these interventions would markedly increase. The primary alternative interpretation of the observational data is that RSV LRTI in early life is a marker of an underlying predisposition for the development of RWEC and asthma. If this is the case, RSV vaccines and mAbs would not necessarily be expected to impact these outcomes. To evaluate whether the available evidence supports a causal association between RSV LRTI and RWEC/asthma and to provide guidance for future studies, the World Health Organization convened a meeting of subject matter experts on February 12–13, 2019 in Geneva, Switzerland. After discussing relevant background information and reviewing the current epidemiologic evidence, the group determined that: (i) the evidence is inconclusive in establishing a causal association between RSV LRTI and RWEC/asthma, (ii) the evidence does not establish that RSV mAbs (and, by extension, future vaccines) will have a substantial effect on these outcomes and (iii) regardless of the association with long-term childhood respiratory morbidity, severe acute RSV disease in young children poses a substantial public health burden and should continue to be the primary consideration for policy-setting bodies deliberating on RSV vaccine and mAb recommendations. Nonetheless, the group recognized the public health importance of resolving this question and suggested good practice guidelines for future studies. Copyright 2020 Elsevier Ltd
    • Ebola vaccination in the Democratic Republic of the Congo

      Wells, Chad R.; Pandey, Abhishek; Fitzpatrick, Meagan C. (2019-05-14)
      Following the April 2018 reemergence of Ebola in a rural region of the Democratic Republic of the Congo (DRC), the virus spread to an urban center by early May. Within 2 wk of the first case confirmation, a vaccination campaign was initiated in which 3,017 doses were administered to contacts of cases and frontline healthcare workers. To evaluate the spatial dynamics of Ebola transmission and quantify the impact of vaccination, we developed a geographically explicit model that incorporates high-resolution data on poverty and population density. We found that while Ebola risk was concentrated around sites initially reporting infections, longer-range dissemination also posed a risk to areas with high population density and poverty. We estimate that the vaccination program contracted the geographical area at risk for Ebola by up to 70.4% and reduced the level of risk within that region by up to 70.1%. The early implementation of vaccination was critical. A delay of even 1 wk would have reduced these effects to 33.3 and 44.8%, respectively. These results underscore the importance of the rapid deployment of Ebola vaccines during emerging outbreaks to containing transmission and preventing global spread. The spatiotemporal framework developed here provides a tool for identifying high-risk regions, in which surveillance can be intensified and preemptive control can be implemented during future outbreaks.
    • How can controlled human infection models accelerate clinical development and policy pathways for vaccines against Shigella?

      Giersing, Birgitte K.; Porter, Chad K.; Kotloff, Karen L. (Elsevier Ltd., 2019-08-07)
      Controlled Human Infection Models (CHIMs) now exist for several infectious diseases. CHIMs offer significant insight into disease pathogenesis, as well the potential to rapidly test clinical proof-of-concept of vaccine candidates. The application of CHIMs to identify a correlate of protection that may reduce the sample size of, or obviate the need for clinical efficacy studies to achieve licensure is of considerable interest to vaccine developers and public health stakeholders. This topic was the subject of a workshop at the 2018 Vaccines Against Shigella and ETEC (VASE) conference, in the context of O-antigen-based Shigella vaccines. © 2019 The Authors
    • Humanized mice in dengue research: A comparison with other mouse models

      Medina-Moreno, S.; Chua, J.V.; Zapata, J.C. (MDPI AG, 2020)
      Dengue virus (DENV) is an arbovirus of the Flaviviridae family and is an enveloped virion containing a positive sense single-stranded RNA genome. DENV causes dengue fever (DF) which is characterized by an undifferentiated syndrome accompanied by fever, fatigue, dizziness, muscle aches, and in severe cases, patients can deteriorate and develop life-threatening vascular leakage, bleeding, and multi-organ failure. DF is the most prevalent mosquito-borne disease affecting more than 390 million people per year with a mortality rate close to 1% in the general population but especially high among children. There is no specific treatment and there is only one licensed vaccine with restricted application. Clinical and experimental evidence advocate the role of the humoral and T-cell responses in protection against DF, as well as a role in the disease pathogenesis. A lot of pro-inflammatory factors induced during the infectious process are involved in increased severity in dengue disease. The advances in DF research have been hampered by the lack of an animal model that recreates all the characteristics of this disease. Experiments in nonhuman primates (NHP) had failed to reproduce all clinical signs of DF disease and during the past decade, humanized mouse models have demonstrated several benefits in the study of viral diseases affecting humans. In DENV studies, some of these models recapitulate specific signs of disease that are useful to test drugs or vaccine candidates. However, there is still a need for a more complete model mimicking the full spectrum of DENV. This review focuses on describing the advances in this area of research. Copyright 2020 by the authors.
    • Informing randomized clinical trials of respiratory syncytial virus vaccination during pregnancy to prevent recurrent childhood wheezing: A sample size analysis

      Riddell, C.A.; Bhat, N.; Bont, L.J. (Elsevier Ltd, 2018)
      Background: Early RSV illness is associated with wheeze-associated disorders in childhood. Candidate respiratory syncytial virus (RSV) vaccines may prevent acute RSV illness in infants. We investigated the feasibility of maternal RSV vaccine trials to demonstrate reductions in recurrent childhood wheezing in general paediatric populations. Methods: We calculated vaccine trial effect sizes that depended on vaccine efficacy, allocation ratio, rate of early severe RSV illness, risk of recurrent wheezing at age 3, and increased risk of RSV infection on recurrent wheezing. Model inputs came from systematic reviews and meta-analyses. For each combination of inputs, we estimated the sample size required to detect the effect of vaccination on recurrent wheezing. Results: There were 81 scenarios with 1:1 allocation ratio. Risk ratios between vaccination and recurrent wheezing ranged from 0.9 to 1.0 for 70% of the scenarios. Among the 57 more plausible scenarios, the lowest sample size required to detect significant reductions in recurrent wheezing was 6196 mother-infant pairs per trial arm; however, 75% and 47% of plausible scenarios required >31,060 and >100,000 mother-infant pairs per trial arm, respectively. Studies with asthma endpoints at age 5 will likely need to be larger. Discussion: Clinical efficacy trials of candidate maternal RSV vaccines undertaken for licensure are unlikely to demonstrate an effect on recurrent wheezing illness due to the large sample sizes likely needed to demonstrate a significant effect. Further efforts are needed to plan for alternative study designs to estimate the impact of maternal RSV vaccine programs on recurrent childhood wheezing in general populations. Copyright 2018 The Author(s)
    • Pharmacotherapeutics of SARS-CoV-2 Infections

      Kevadiya, Bhavesh D; Machhi, Jatin; Herskovitz, Jonathan; Oleynikov, Maxim D; Blomberg, Wilson R; Bajwa, Neha; Soni, Dhruvkumar; Das, Srijanee; Hasan, Mahmudul; Patel, Milankumar; et al. (Springer Nature, 2021-01-06)
      The COVID-19 pandemic has affected more than 38 million people world-wide by person to person transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therapeutic and preventative strategies for SARS-CoV-2 remains a significant challenge. Within the past several months, effective treatment options have emerged and now include repurposed antivirals, corticosteroids and virus-specific antibodies. The latter has included convalescence plasma and monoclonal antibodies. Complete viral eradication will be achieved through an effective, safe and preventative vaccine. To now provide a comprehensive summary for each of the pharmacotherapeutics and preventative strategies being offered or soon to be developed for SARS-CoV-2. Graphical abstract: [Figure not available: see fulltext.].
    • Reaching every child with rotavirus vaccine: Report from the 10th African rotavirus symposium held in Bamako, Mali

      Sow, S.O.; Steele, A.D.; Mwenda, J.M. (Elsevier Ltd, 2017)
      The Center for Vaccine Development – Mali (CVD – Mali), the World Health Organization’s regional office in Africa (WHO/AFRO), and the CVD at the University of Maryland School of Medicine hosted the 10th African Rotavirus Symposium in Bamako, Mali on 1–2 June 2016. The symposium is coordinated by WHO/AFRO, the Regional Rotavirus Reference Laboratories, and the African Rotavirus Network (ARN), with support from the Bill & Melinda Gates Foundation. The event brings together leading rotavirus researchers, scientists, and policy-makers from across Africa and the world. Over 150 participants, from 31 countries, including 27 in Africa, joined forces to address the theme “Reaching Every Child in Africa with Rotavirus Vaccines.” This symposium, the first in francophone Africa, occurred at an unprecedented time when 33 African countries had introduced rotavirus vaccines into their national immunization programs. The symposium concluded with a Call to Action to introduce rotavirus vaccines in the 21 remaining African countries, to increase access in countries with existing vaccination programs, and to continue surveillance and research on rotavirus and other diarrheal diseases. Copyright 2017
    • Rotavirus vaccine effectiveness in low-income settings: An evaluation of the test-negative design

      Schwartz, L.M.; Halloran, M.E.; Rowhani-Rahbar, A. (Elsevier Ltd, 2017)
      Background The test-negative design (TND), an epidemiologic method currently used to measure rotavirus vaccine (RV) effectiveness, compares the vaccination status of rotavirus-positive cases and rotavirus-negative controls meeting a pre-defined case definition for acute gastroenteritis. Despite the use of this study design in low-income settings, the TND has not been evaluated to measure rotavirus vaccine effectiveness. Methods This study builds upon prior methods to evaluate the use of the TND for influenza vaccine using a randomized controlled clinical trial database. Test-negative vaccine effectiveness (VE-TND) estimates were derived from three large randomized placebo-controlled trials (RCTs) of monovalent (RV1) and pentavalent (RV5) rotavirus vaccines in sub-Saharan Africa and Asia. Derived VE-TND estimates were compared to the original RCT vaccine efficacy estimates (VE-RCTs). The core assumption of the TND (i.e., rotavirus vaccine has no effect on rotavirus-negative diarrhea) was also assessed. Results TND vaccine effectiveness estimates were nearly equivalent to original RCT vaccine efficacy estimates. Neither RV had a substantial effect on rotavirus-negative diarrhea. Conclusions This study supports the TND as an appropriate epidemiologic study design to measure rotavirus vaccine effectiveness in low-income settings. Copyright 2016 The Author(s)
    • Safety and immunogenicity of an HIV-1 gp120-CD4 chimeric subunit vaccine in a phase 1a randomized controlled trial

      Chua, Joel V; Davis, Charles; Husson, Jennifer S; Nelson, Amy; Prado, Ilia; Flinko, Robin; Lam, Ka Wing J; Mutumbi, Lydiah; Mayer, Bryan T; Dong, Dan; et al. (Elsevier Ltd., 2021-06-04)
      A major challenge for HIV vaccine development is to raise anti-envelope antibodies capable of recognizing and neutralizing diverse strains of HIV-1. Accordingly, a full length single chain (FLSC) of gp120-CD4 chimeric vaccine construct was designed to present a highly conserved CD4-induced (CD4i) HIV-1 envelope structure that elicits cross-reactive anti-envelope humoral responses and protective immunity in animal models of HIV infection. IHV01 is the FLSC formulated in aluminum phosphate adjuvant. We enrolled 65 healthy adult volunteers in this first-in-human phase 1a randomized, double-blind, placebo-controlled study with three dose-escalating cohorts (75 µg, 150 µg, and 300 µg doses). Intramuscular injections were given on weeks 0, 4, 8, and 24. Participants were followed for an additional 24 weeks after the last immunization. The overall incidence of adverse events (AEs) was not significantly different between vaccinees and controls. The majority (89%) of vaccine-related AE were mild. The most common vaccine-related adverse event was injection site pain. There were no vaccine-related serious AE, discontinuation due to AE, intercurrent HIV infection, or significant decreases in CD4 count. By the final vaccination, all vaccine recipients developed antibodies against IHV01 and demonstrated anti-CD4i epitope antibodies. The elicited antibodies reacted with CD4 non-liganded Env antigens from diverse HIV-1 strains. Antibody-dependent cell-mediated cytotoxicity against heterologous infected cells or gp120 bound to CD4+ cells was evident in all cohorts as were anti-gp120 T-cell responses. IHV01 vaccine was safe, well tolerated, and immunogenic at all doses tested. The vaccine raised broadly reactive humoral responses against conserved CD4i epitopes on gp120 that mediates antiviral functions.
    • The SENIEUR protocol and the efficacy of hepatitis B vaccination in healthy elderly persons by age, gender, and vaccine route

      Edelman, R.; Deming, M.E.; Toapanta, F.R.; Heuser, M.D.; Chrisley, L.; Barnes, R.S.; Wasserman, S.S.; Handwerger, B.S.; Pasetti, M.; Sztein, M.B. (BioMed Central Ltd., 2020)
      Background: Reduced response to hepatitis B vaccines is associated with aging, confounding and comorbid conditions, as well as inadvertent subcutaneous (SC) inoculation. We hypothesized that the antibody and T cell-mediated immune responses (T-CMI) of elderly adults to a vaccine intended for intramuscular (IM) administration would be attenuated when deposited into SC fat, independent of confounding conditions. Results: Fifty-two healthy, community dwelling elderly adults (65-82 years), seronegative for HBV, were enrolled in the SENIEUR protocol as a strictly healthy population. These seniors were randomized to receive a licensed alum-adjuvanted recombinant HBV vaccine either SC or IM, with the inoculum site verified by imaging. The response rates, defined as hepatitis B surface antibodies (HBsAb) ?10 IU/L, were significantly lower in the elderly than in young adults, a group of 12, healthy, 21-34-year-old volunteers. Moreover, elderly participants who received the vaccine IM were significantly more likely to be responders than those immunized SC (54% versus 16%, p = 0.008). The low seroconversion rate in the IM group progressively declined with increasing age, and responders had significantly lower HBsAb titers and limited isotype responses. Moreover, T-CMI (proliferation and cytokine production) were significantly reduced in both percentage of responders and intensity of the response for both Th1 and Th2 subsets in the elderly. Conclusions: Our data demonstrate the blunted immunogenicity of SC inoculation as measured by peak titers and response rates. Further, the qualitative and quantitative deficits in B- A nd T-CMI responses to primary alum adjuvanted protein antigens persisted even in strictly healthy elderly populations with verified IM placement compared to younger populations. Clinical trial registration: ClinicalTrials.gov, NCT04162223. Registered 14 November 2019. Retrospectively registered. Copyright 2020 The Author(s).
    • Structural basis for epitopes in the gp120 cluster a region that invokes potent effector cell activity

      Tolbert, W.D.; Sherburn, R.T.; Van, V. (MDPI AG, 2019)
      While a number of therapeutic options to control the progression of human immunodeficiency virus (HIV-1) now exist, a broadly effective preventive vaccine is still not available. Through detailed structural analysis of antibodies able to induce potent effector cell activity, a number of Env epitopes have been identified which have the potential to be considered vaccine candidates. These antibodies mainly target the gp120 Cluster A region which is only exposed upon viral binding to the target cell with epitopes becoming available for antibody binding during viral entry and fusion and, therefore, after the effective window for neutralizing antibody activity. This review will discuss recent advances in the structural characterization of these important targets with a special focus on epitopes that are involved in Fc-mediated effector function without direct viral neutralizing activities. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.