Effective Human Immunodeficiency Virus Vaccine Research Articles

Application of Memory Natural Killer Cells in HIV Vaccine

Human immunodeficiency virus (HIV) is a formidable infection targeting the intricate defense mechanisms of the human body, primarily focusing its assault on the vital white blood cells known as CD4 cells. HIV impairs these CD4 cells, reducing resistance to opportunistic infections. In 2022, 630,000 people died from HIV-related causes globally due to the lack of preventative vaccines and effective treatment. The pursuit of an effective HIV vaccine remains a critical endeavor in global health, necessitating innovative strategies that can elicit robust and durable immune responses. Natural killer (NK) cells, renowned for their swift and inherent cytotoxic prowess, constitute a critical element of innate immunity, typically thought to be deficient in memory abilities. Fascinatingly, NK cells have now become the focal point of scientific research due to emerging evidence suggesting the presence of memory-like characteristics within their functional repertoire. Through a comprehensive exploration of NK cell subpopulations and the strategic application of cytokines or other stimuli to induce the development of memory-generating NK cell subpopulations, the potential for enhancing the efficacy of HIV vaccines emerges. This approach holds promise in bolstering the creation of adaptive immunity and advancing the quest for effective HIV immunization strategies. The study offers valuable insights into the potential of NK memory cells as a viable component of future HIV vaccine regimens, suggesting avenues for further research and development in the quest to mitigate the global burden of HIV.

Major HIV vaccine candidates

Introduction and objective: Human immunodeficiency virus (HIV) is a virus, which is responsible for an acquired immunodeficiency syndrome (AIDS). This pathogen is widespread worldwide causing a pandemic that has been going on for decades. Researches around the world are trying to end this situation and it seems that the greatest hope lies in finding an effective vaccine. It is important due to the fact that AIDS and its consequences are responsible even nowadays for death of many people infected around the world. The aim of this study was to provide the most important information about major HIV vaccine trials and efficacy of vaccine candidates.
 Materials and methods: For the purposes of writing this article, the available literature was reviewed. The database of medical publications – Pubmed datebase and other publicaly available books, database and online sites was searched, with the use of keywords such as HIV, HIV vaccine, HIV epidemiology.
 State of knowledge: According to review studies HIV vaccine trials has been going for 4 decades. Over 250 trials has been conducted since then, but unfortunately, none of them resulted in effective vaccine. The difficulties of this task are mainly connected with the nature of HIV virus. To date, one study has shown some effectiveness, but not enough to claim success. Other studies are ongoing around the world and more are planned.
 Conclusions: Developing an effective HIV vaccine is the clue to solving the problem, which is new HIV infections. Further researches, further research funding and international cooperation are needed to end this pandemic.

Paradigms in HIV vaccine research

Although a large number of preventative human immunodeficiency virus (HIV) vaccine trials have been carried out during the last 30 years, it is remarkable that an effective HIV vaccine has not yet been developed. Research paradigms correspond to theoretical assumptions and particular strategies that scientists use when they try to solve a particular problem. Many paradigms used successfully in vaccinology were ineffective with HIV. For instance: 1) The structure-based reverse vaccinology approach failed because investigators tried to generate a vaccine starting with the antigenic structure of HIV-envelope (Env) epitopes bound to neutralizing monoclonal antibodies (mAbs) derived from HIV-infected individuals. They assumed that this antigenic structure would also possess the immunogenic capacity of inducing in vaccinees a polyclonal antibody (Ab) response with the same neutralizing capacity as the mAb. 2) The structures observed in epitope-paratope crystallographic complexes result from mutually induced fit between the two partners and do not correspond to the structures present in the free molecules before they had interacted. 3) The affinity-matured neutralizing mAbs obtained from chronically infected individuals did not recognize the germline predecessors of these Abs present in vaccinees. 4) The HIV p17 matrix protein that lines the inner surface of the viral membrane is one of the most disordered proteins identified on our planet and this prevents the induced Abs from binding to the glycosylated HIV gp120 protein. 5) Vaccinologists need to solve so-called inverse problems, for instance, guessing what are the multiple causes that produced an earlier wanted beneficial effect such as the absence of deleterious HIV infection in elite controllers. Since the immune system consists of numerous subsystems that have not yet been elucidated, it is impossible to solve the inverse problems posed by each subsystem. 6) Vaccinology is an empirical science that only sometimes succeeds because we do not understand the complex mechanisms that lead to protective immune responses.

An Update on the HIV DNA Vaccine Strategy

In 2020, the global prevalence of human immunodeficiency virus (HIV) infection was estimated to be 38 million, and a total of 690,000 people died from acquired immunodeficiency syndrome (AIDS)–related complications. Notably, around 12.6 million people living with HIIV/AIDS did not have access to life-saving treatment. The advent of the highly active antiretroviral therapy (HAART) in the mid-1990s remarkably enhanced the life expectancy of people living with HIV/AIDS as a result of improved immune functions. However, HAART has several drawbacks, especially when it is not used properly, including a high risk for the development of drug resistance, as well as undesirable side effects such as lipodystrophy and endocrine dysfunctions, which result in HAART intolerability. HAART is also not curative. Furthermore, new HIV infections continue to occur globally at a high rate, with an estimated 1.7 million new infections occurring in 2018 alone. Therefore, there is still an urgent need for an affordable, effective, and readily available preventive vaccine against HIV/AIDS. Despite this urgent need, however, progress toward an effective HIV vaccine has been modest over the last four decades. Reasons for this slow progress are mainly associated with the unique aspects of HIV itself and its ability to rapidly mutate, targeting immune cells and escape host immune responses. Several approaches to an HIV vaccine have been undertaken. However, this review will mainly discuss progress made, including the pre-clinical and clinical trials involving vector-based HIV DNA vaccines and the use of integrating lentiviral vectors in HIV vaccine development. We concluded by recommending particularly the use of integrase-defective lentiviral vectors, owing to their safety profiles, as one of the promising vectors in HIV DNA vaccine strategies both for prophylactic and therapeutic HIV vaccines.

Evaluation of novel HIV vaccine candidates using recombinant vesicular stomatitis virus vector produced in serum-free Vero cell cultures

Acquired Immune Deficiency Syndrome (AIDS) in humans is a result of the destruction of the immune system caused by Human Immunodeficiency Virus (HIV) infection. This serious epidemic is still progressing world-wide. Despite advances in treatment, a safe and effective preventive HIV vaccine is desired to combat this disease, and to save millions of lives. However, such a vaccine is not available yet although extensive amounts of resources in research and development have been invested over three decades. In light of the recently approved Ebola virus disease vaccine based on a recombinant vesicular stomatitis virus (rVSV-ZEBOV), we present the results of our work on three novel VSV-vectored HIV vaccine candidates. We describe the design, rescue, production and purification method and evaluate their immunogenicity in mice prior to preclinical studies that will be performed in non-human primates. The production of each of the three candidate vaccines (rVSV-B6-NL4.3Env/SIVtm, rVSV-B6-NL4.3Env/Ebtm and rVSV-B6-A74Env(PN6)/SIVtm) was evaluated in small scale in Vero cells and it was found that production kinetics on Vero cells vary depending on the HIV gp surface protein used. Purified virus preparations complied with the WHO restrictions for the residual DNA and host cell protein contents. Finally, when administered to mice, all three rVSV-HIV vaccine candidates induced an HIV gp140-specific antibody response.

Development and Preclinical Evaluation of an Integrase Defective Lentiviral Vector Vaccine Expressing the HIVACAT T Cell Immunogen in Mice

Cellular immune responses play a fundamental role in controlling viral replication and AIDS progression in human immunodeficiency virus (HIV)-infected subjects and in simian immunodeficiency virus (SIV)-infected macaques. Integrase defective lentiviral vector (IDLV) represents a promising vaccine candidate, inducing functional and durable immune responses in mice and non-human primates. Here, we designed HIV- and SIV-based IDLVs to express the HIVACAT T cell immunogen (HTI), a mosaic antigen designed to cover vulnerable sites in HIV-1 Gag, Pol, Vif, and Nef. We observed that HTI expression during lentiviral vector production interfered profoundly with IDLV particles release because of sequestration of both HIV- and SIV-Gag proteins in the cytoplasm of the vector-producing cells. However, modifications in IDLV design and vector production procedures greatly improved recovery of both HIV- and SIV-based IDLV-HTI. Immunization experiments in BALB/c mice showed that both IDLVs elicited HTI-specific T cell responses. However, immunization with HIV-based IDLV elicited also a T cell response toward exogenous HIV proteins in IDLV particles, suggesting that SIV-based IDLV may be a preferable platform to assess the induction of transgene-specific immune responses against rationally designed HIV structural antigens. These data support the further evaluation of IDLV as an effective platform of T cell immunogens for the development of an effective HIV vaccine.

Development of a human leukocyte antigen-based HIV vaccine.

Human immunodeficiency virus (HIV) carries abundant human cell proteins, particularly human leukocyte antigen (HLA) molecules when the virus leaves host cells. Immunization in macaques with HLAs protects the animals from simian immunodeficiency virus infection. This finding offers an alternative approach to the development of HLA molecule-based HIV vaccines. Decades of studies have enhanced a great deal of our understanding of the mechanisms of allo-immune response-mediated anti-HIV immunity. These include cell-mediated immunity, innate immunity, and antibody response. These studies provided a rationale for the future design of effective HIV vaccines.

Biophysical Studies of Liposome Encapsulated Pokeweed Antiviral Protein and its use as a HIV Therapeutic

Human Immunodeficiency Virus (HIV) is a virus that attacks the human immune system, compromising its effect in regards to disease prevention. HIV results in the destruction of CD4 cells, which are vital in the defense against human immune responses. HIV can severely damage the immune system and lead to Acquired Immunodeficiency Syndrome (AIDS). There is presently no cure or effective HIV vaccine and as a result it is important to seek alternative measures in the defense against HIV/AIDS. Pokeweed Antiviral Protein (PAP), a protein isolated from pokeweed plant, Phytolacca americana, provides a new and profoundly promising direction in the field of HIV/AIDS research. PAP plays a vital role in the immune system of pokeweed and is a ribosome inactivating protein (RIP), inhibiting viral protein production. PAP possesses antiviral properties, and reduces the infectivity of many plant and animal viruses, including HIV-1. My project focuses on mechanisms using liposomal encapsulated PAP, targeted to infected cells as a therapeutic for HIV infection. Steady state fluorescence was used to identify the thermodynamic parameters of interaction between PAP and HIV RNA. PAP binds to the m7 GTP cap and the 5′ UTR region of HIV RNA. Various isoforms of PAP were tested and the optimal affinity was identified as a Km of 20.09 nM. Fluorescence observed V.S [m7 GTP] was plotted through nonlinear regression using the Prism 6.0 program. Varying liposomes were prepared in order to identify the optimal characteristics for PAP encapsulation. Liposomes were lyophilized through rotary evaporation and later extruded to ensure homogeneity. Fluorescent titration enables the testing of liposomal PAP encapsulation efficiency. It was concluded that a 1/1 v% mixture of liposomes DOPE-DOTAP is most efficient for PAP encapsulation. These accomplishments will enable further modification of the liposomes by covalently conjugating HIV-specific monoclonal antibodies (anti-pg120 and/or anti-pg41), thus facilitating the selectivity of the liposomal PAP to the target tissues (HIV-infected CD4+ lymphocytes). With the aforementioned completed the basis for PAP-liposome interactions can be established and also the modulation of these interactions in order to target HIV-infected cells.

B-cell responses to HIV infection.

The induction of neutralizing antibodies directed against the human immunodeficiency virus (HIV) has received considerable attention in recent years, in part driven by renewed interest and opportunities for antibody-based strategies for prevention such as passive transfer of antibodies and the development of preventive vaccines, as well as immune-based therapeutic interventions. Advances in the ability to screen, isolate, and characterize HIV-specific antibodies have led to the identification of a new generation of potent broadly neutralizing antibodies (bNAbs). The majority of these antibodies have been isolated from B cells of chronically HIV-infected individuals with detectable viremia. In this review, we provide insight into the phenotypic and functional attributes of human B cells, with a focus on HIV-specific memory B cells and plasmablasts/cells that are responsible for sustaining humoral immune responses against HIV. We discuss the abnormalities in B cells that occur in HIV infection both in the peripheral blood and lymphoid tissues, especially in the setting of persisting viremia. Finally, we consider the opportunities and drawbacks of intensively interrogating antibodies isolated from HIV-infected individuals to guide strategies aimed at developing effective antibody-based vaccine and therapeutic interventions for HIV.

Virus-Like Particles Displaying Trimeric Simian Immunodeficiency Virus (SIV) Envelope gp160 Enhance the Breadth of DNA/Modified Vaccinia Virus Ankara SIV Vaccine-Induced Antibody Responses in Rhesus Macaques.

The encouraging results of the RV144 vaccine trial have spurred interest in poxvirus prime-protein boost human immunodeficiency virus (HIV) vaccine modalities as a strategy to induce protective immunity. Because vaccine-induced protective immunity is critically determined by HIV envelope (Env) conformation, significant efforts are directed toward generating soluble trimeric Env immunogens that assume native structures. Using the simian immunodeficiency virus (SIV)-macaque model, we tested the immunogenicity and efficacy of sequential immunizations with DNA (D), modified vaccinia virus Ankara (MVA) (M), and protein immunogens, all expressing virus-like particles (VLPs) displaying membrane-anchored trimeric Env. A single VLP protein boost displaying trimeric gp160 adjuvanted with nanoparticle-encapsulated Toll-like receptor 4/7/8 (TLR4/7/8) agonists, administered 44 weeks after the second MVA immunization, induced up to a 3-fold increase in Env-specific IgG binding titers in serum and mucosa. Importantly, the VLP protein boost increased binding antibody against scaffolded V1V2, antibody-dependent phagocytic activity against VLP-coated beads, and antibody breadth and neutralizing antibody titers against homologous and heterologous tier 1 SIVs. Following 5 weekly intrarectal SIVmac251 challenges, two of seven DNA/MVA and VLP (DM+VLP)-vaccinated animals were completely protected compared to productive infection in all seven DM-vaccinated animals. Vaccinated animals demonstrated stronger acute viral pulldown than controls, but a trend for higher acute viremia was observed in the DM+VLP group, likely due to a slower recall of Gag-specific CD8 T cells. Our findings support immunization with VLPs containing trimeric Env as a strategy to augment protective antibody but underscore the need for optimal engagement of CD8 T cells to achieve robust early viral control. The development of an effective HIV vaccine remains a global necessity for preventing HIV infection and reducing the burden of AIDS. While this goal represents a formidable challenge, the modest efficacy of the RV144 trial indicates that multicomponent vaccination regimens that elicit both cellular and humoral immune responses can prevent HIV infection in humans. However, whether protein immunizations synergize with DNA prime-viral vector boosts to enhance cellular and humoral immune responses remains poorly understood. We addressed this question in a nonhuman primate model, and our findings show benefit for sequential protein immunization combined with a potent adjuvant in boosting antibody titers induced by a preceding DNA/MVA immunization. This promising strategy can be further developed to enhance neutralizing antibody responses and boost CD8 T cells to provide robust protection and viral control.

Recent update in HIV vaccine development.

Despite the tremendous efforts to develop a successful human immunodeficiency virus (HIV) vaccine, the quest for a safe and effective HIV vaccine seems to be remarkably long and winding. Disappointing results from previous clinical trials of VaxGen's AIDSVAXgp120 vaccine and MRKAd5 HIV-1 Gag/Pol/Nef vaccine emphasize that understanding the correlates of immune protection in HIV infection is the key to solve the puzzle. The modest vaccine efficacy from RV144 trial and the successive results obtained from the correlate of risk analysis have reinvigorated the HIV vaccine research field leading to various novel strategies. This paper will review the brief history and recent advances in HIV vaccine development.

Editorial: Why Vaccines to HIV, HCV, and Malaria Have So Far Failed-Challenges to Developing Vaccines Against Immunoregulating Pathogens.

Editorial: Why Vaccines to HIV, HCV, and Malaria Have So Far Failed-Challenges to Developing Vaccines Against Immunoregulating Pathogens.

Strategies for preventing mucosal cell-associated HIV transmission.

Human immunodeficiency virus (HIV) may be transmitted through either cell-free virions or leukocytes harboring intracellular HIV in bodily fluids. In recent years, the early initiation of combination antiretroviral therapy leading to virological suppression has resulted in decreased HIV transmission to uninfected partners. Additionally, the efficacy of primary chemoprophylaxis with oral or topical antiretroviral regimens containing tenofovir (with or without emtricitabine) has been demonstrated. However, the efficacy of these approaches may be compromised by suboptimal adherence, decreased drug concentrations in mucosal compartments in women, and genital inflammation. Furthermore, in vitro studies on the effects of tenofovir on cell-associated HIV transmission have produced conflicting results. Preclinical studies suggest that combination preventive approaches may be most effective in stopping the transmission of HIV after mucosal exposure. Since the development of antibodies were found to correlate with protection in the only effective HIV vaccine trial, the administration of preformed mucosal and systemic antibodies may inform the development of safe and effective antibody-based oral, topical, and/or systemic preexposure prophylaxis agents and provide guidance in the development of HIV vaccines that effectively block cell-associated HIV transmission.

Ending the global HIV/AIDS pandemic: the critical role of an HIV vaccine.

While the human immunodeficiency virus (HIV)/AIDS pandemic continues, the incidence of HIV infections has fallen because of the deployment of antiretroviral drugs and multiple prevention modalities. To achieve a durable end to the pandemic, a vaccine remains essential. Recent advances in vaccinology offer new promise for an effective HIV vaccine.

A review on human immunodeficiency virus (HIV) strain candidate vaccine development: Prospect and challenges

Human immunodeficiency virus (HIV) has one of the highest incidence and mortality rates of any infectious disease, with more than 33 million people infected worldwide. Specifically, HIV causes the destruction of helper T cells, ultimately resulting in the suppression of the immune system and leaving its human host susceptible to countless of other pathogenic agents. The development of an effective HIV vaccine has continued for more than 20 years. But the use of preventative vaccines using traditional vaccine technologies, which have proven successful for other diseases, has thus far failed with HIV. One vaccine, AIDSVAX, was the first HIV vaccine to reach a phase III efficacy trial, but has not yet been shown to eradicate HIV. Hope now lies in the development of therapeutic vaccines using novel technologies. One such vaccine is ALVAC-HIV, which when used in conjunction with other vaccines (AIDSVAX or Lipo-6T with IL-2 injections) has shown a great deal of promise in clinical trials suppressing viral replication and improving the immune system. Other therapeutic vaccines, such as Ad5, however, have been unsuccessful. While many believed that developing an effective HIV vaccine is impossible, efforts continue into researching its structure, transmission, immune system suppression, genetic variability, and immune system evasion. As long as research continues, hope remains that someday an effective vaccine will be developed. Key words: Vaccines, human immunodeficiency virus (HIV), acquired immunodeficiency syndrome (AIDS), recombinant, lymphocytes.

Recent Advances in Humanized Mice: Accelerating the Development of an HIV Vaccine

Recent advances in the development of humanized mice hold great promise to advance our understanding of protective immunity to human immunodeficiency virus (HIV) infection and to aid in the design of an effective HIV vaccine. This supplement of the Journal of Infectious Diseases summarizes work in the humanized mouse model presented at an HIV Humanized Mouse workshop in Boston, Massachusetts, in November 2012, including recent advances in the development of humanized mice, the trafficking of human immune cells following mucosal HIV transmission, the role of immune activation and Toll-like receptor agonists in the control of HIV, the induction and efficacy of HIV-specific cellular and humoral immune responses, and the preclinical modeling of novel anti-HIV therapeutics. Many gaps remain in our understanding of how to design an effective HIV vaccine and novel therapeutics to eliminate the viral reservoir. Promising early results from studies in humanized mice suggest great potential and enthusiasm for this model to accelerate these critical areas of HIV research.

Novel HIV vaccine strategies: overview and perspective.

A human immunodeficiency virus (HIV) vaccine remains a central component in the quest to control the worldwide epidemic. To examine the status of the development of HIV vaccines, we review the results of the efficacy trials carried out to date and the immunologic principles that guided them. Four vaccine concepts have been evaluated in HIV-1 vaccine efficacy trials, and the results of these trials have provided significant information for future vaccine development. While one of these trials demonstrated that a safe and effective HIV vaccine is possible, many questions remain regarding the basis for the observed protection and the most efficient way to stimulate it. Novel HIV vaccine strategies including induction of highly potent broadly neutralizing antibodies, use of novel homologous and heterologous vector systems, and vectored immunoprophylaxis seek to expand and build upon the knowledge gained from these trials.

Insights into B cells and HIV‐specific B‐cell responses in HIV‐infected individuals

Human immunodeficiency virus (HIV) disease is associated with dysregulation and dysfunction involving all major lymphocyte populations, including B cells. Such perturbations occur early in the course of infection and are driven in large part by immune activation resulting from ongoing HIV replication leading to bystander effects on B cells. While most of the knowledge regarding immune cell abnormalities in HIV-infected individuals has been gained from studies conducted on the peripheral blood, it is clear that the virus is most active and most damaging in lymphoid tissues. Here, we discuss B-cell perturbations in HIV-infected individuals, focusing on the skewing of B-cell subsets that circulate in the peripheral blood and their counterparts that reside in lymphoid tissues. This review also highlights recent advances in evaluating HIV-specific B-cell responses both in the memory B-cell compartment, as well as in circulating antibody-secreting plasmablasts and the more differentiated plasma cells residing in tissues. Finally, we consider how knowledge gained by investigating B cells in HIV-infected individuals may help inform the development of an effective antibody-based HIV vaccine.

Editorial Commentary: Universal Antiretroviral Therapy for HIV Infection?

Human immunodeficiency virus (HIV) still infects more people per year than existing health systems are able to initiate and maintain on antiretroviral therapy. Therefore, the development of effective HIV population prevention strategies remains a high priority. There is no immediate promise for an effective HIV vaccine, risk behavior change has been difficult to implement, and biomedical prevention measures lack effectiveness due to inconsistent use. In contrast, antiretroviral therapy (ART) can benefit the infected individual and under clinical trial conditions has been shown to reduce transmission [1]. The use of ART as both treatment and prevention is now a well-established concept, which has been widely welcomed as the “missing link” that will curb HIV incidence [2]. However, a disconnect exists between the individual and transmission benefits of ART. Persons with advanced HIV disease (reflected by having a CD4 lymphocyte count <250 cells/μL), have clear benefit, documented by several randomized controlled trials (reviewed in [3]). Conversely, the target populations for transmission benefit are those with high CD4 counts, in whom observational studies have shown inconsistent or no clinical benefit (reviewed in [4]). Additional biological plausibility for early treatment has been the observation that untreated HIV infection activates host inflammatory processes associated with organ disease and cancers and that ART partly (but not completely) reverts immune activation. However, no specific anti-inflammatory intervention has been demonstrated to reduce the risk of these adverse outcomes, and changes in inflammatory biomarker levels have not been validated surrogates for clinical benefits of ART. Therefore, whether inflammation is causally involved in the pathogenesis of these events or merely an epiphenomena to the underlying pathology remains to be identified in HIV as it does in the general population. The uncertainties relating to net benefit of early ART are reflected in disparities between treatment guidelines. Guidelines based on consensus “expert opinion” recommend that all HIV-positive persons, as a matter of principle, should be started on ART [5, 6], and those based on available direct evidence [7–9] (including the 2010 World Health Organization guidelines) are more conservative. Unfortunately, consensus among experts can be prescient or subsequently shown to be incorrect. For example, 10 years ago, expert opinion was that ART could be used intermittently, but the SMART (Strategies for Management of Antiretroviral Therapy) trial demonstrated definitively that this view was wrong [10]. Gallant et al, in this issue of Clinical Infectious Diseases [11], highlight reasons why the recommendations of the US guidelines are not necessarily generalizable to other settings. They highlight a fundamental ethical obligation of clinicians to benefit patients while not causing harm. They note that although the individual benefits of early ART remain undefined in resource-limited settings, the risks associated with early ART may be higher. Cost constraints in resourcelimited settings limit the available ART repertoire, resulting in frequent use of older, cheaper drugs with poor adverse event profiles. In a setting where only stavudine-based ART regimens are available, for example, starting ART at a high CD4 count of 650 cells/μL would less likely maintain health than deferring to a more conservative threshold of 250–350 cells/μL. Lack of laboratory monitoring may also potentially increase risk by delayed recognition of toxicity. Tenofovir, which is included in most currently recommended ART regimens, may adversely affect kidney and bone physiology [12, 13]. Emerging reports of more severe renal diseases in settings without access to laboratory monitoring raise Received 30 May 2013; accepted 1 June 2013; electronically published 11 June 2013. Correspondence: Jens D. Lundgren, MD, DMSc, Department of Infectious Diseases (5112), Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen O, Denmark (jdl@cphiv.dk). Clinical Infectious Diseases 2013;57(6):888–90 © The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals. permissions@oup.com. DOI: 10.1093/cid/cit381

Challenges on Induction of Broadly Neutralizing Antibodies for Optimization of HIV Vaccines Development and Vectored Immunoprophylaxis

Despite extensive research efforts, a preventive human immunodeficiency virus (HIV) vaccine remains one of the major challenges in the field of AIDS research. Experimental strategies which have been proven successful for other viral vaccines are not enough to tackle HIV-1 and new approaches to design effective preventive AIDS vaccines are of utmost importance. Due to enormous diversity among global circulating HIV strains, an effective HIV vaccine must elicit broadly protective antibodies based responses; therefore discovering new broadly neutralizing antibodies (bNAbs) against HIV has become major focus in HIV vaccine research. However further understanding of the viral targets of such antibodies and mechanisms of action of bNAbs is required for advancement of HIV vaccine research. This technical note discusses our current knowledge on the bNAbs and immunoprophylaxis using viral vectors with their relevance in designing of new candidates to HIV-1 vaccines.