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Frontiers in Immunology 2020Following the discovery of HIV as a causative agent of AIDS, the expectation was to rapidly develop a vaccine; but thirty years later, we still do not have a licensed... (Review)
Review
Following the discovery of HIV as a causative agent of AIDS, the expectation was to rapidly develop a vaccine; but thirty years later, we still do not have a licensed vaccine. Progress has been hindered by the extensive genetic variability of HIV and our limited understanding of immune responses required to protect against HIV acquisition. Nonetheless, valuable knowledge accrued from numerous basic and translational science research studies and vaccine trials has provided insight into the structural biology of the virus, immunogen design and novel vaccine delivery systems that will likely constitute an effective vaccine. Furthermore, stakeholders now appreciate the daunting scientific challenges of developing an effective HIV vaccine, hence the increased advocacy for collaborative efforts among academic research scientists, governments, pharmaceutical industry, philanthropy, and regulatory entities. In this review, we highlight the history of HIV vaccine development efforts, highlighting major challenges and future directions.
Topics: AIDS Vaccines; Animals; Antibodies, Neutralizing; Drug Development; HIV; HIV Infections; History, 20th Century; History, 21st Century; Humans; T-Lymphocytes
PubMed: 33193428
DOI: 10.3389/fimmu.2020.590780 -
Nature Reviews. Immunology Feb 2019Of any pathogen, HIV provides perhaps the greatest challenge to successful vaccine development. Nevertheless, progress continued to be made in 2018; new vaccine concepts... (Review)
Review
Of any pathogen, HIV provides perhaps the greatest challenge to successful vaccine development. Nevertheless, progress continued to be made in 2018; new vaccine concepts entered the clinic and new insights were obtained in basic research that will ultimately help to guide rational vaccine design against many’difficult’ pathogens.
Topics: AIDS Vaccines; Animals; HIV; Humans; Vaccinology
PubMed: 30560910
DOI: 10.1038/s41577-018-0103-6 -
Toxins Feb 2022Different mechanisms mediate the toxicity of RNA. Genomic retroviral mRNA hijacks infected host cell factors to enable virus replication. The viral genomic RNA of the... (Review)
Review
Different mechanisms mediate the toxicity of RNA. Genomic retroviral mRNA hijacks infected host cell factors to enable virus replication. The viral genomic RNA of the human immunodeficiency virus (HIV) encompasses nine genes encoding in less than 10 kb all proteins needed for replication in susceptible host cells. To do so, the genomic RNA undergoes complex alternative splicing to facilitate the synthesis of the structural, accessory, and regulatory proteins. However, HIV strongly relies on the host cell machinery recruiting cellular factors to complete its replication cycle. Antiretroviral therapy (ART) targets different steps in the cycle, preventing disease progression to the acquired immunodeficiency syndrome (AIDS). The comprehension of the host immune system interaction with the virus has fostered the development of a variety of vaccine platforms. Despite encouraging provisional results in vaccine trials, no effective vaccine has been developed, yet. However, novel promising vaccine platforms are currently under investigation.
Topics: AIDS Vaccines; Anti-Retroviral Agents; HIV; HIV Infections; Humans; Virus Replication
PubMed: 35202165
DOI: 10.3390/toxins14020138 -
Clinical Pharmacology and Therapeutics Dec 2018Human immunodeficiency virus (HIV) has infected 76 million people and killed an estimated 35 million. During its 40-year history, remarkable progress has been made on... (Review)
Review
Human immunodeficiency virus (HIV) has infected 76 million people and killed an estimated 35 million. During its 40-year history, remarkable progress has been made on antiretroviral drugs. Progress toward a vaccine has also been made, although this has yet to deliver a licensed product. In 2007, I wrote a review, HIV AIDS Vaccines: 2007. This review, HIV AIDS Vaccines: 2018, focuses on the progress in the past 11 years. I begin with key challenges for the development of an AIDS vaccine and the lessons learned from the six completed efficacy trials, only one of which has met with some success.
Topics: AIDS Vaccines; Animals; Antibodies, Neutralizing; Clinical Trials as Topic; Drug Development; Genotype; HIV Antibodies; HIV Antigens; HIV Infections; HIV-1; Host-Pathogen Interactions; Humans; Mutation; Phenotype; Research Design
PubMed: 30099743
DOI: 10.1002/cpt.1208 -
Viruses Apr 2018An efficacious HIV-1 vaccine is regarded as the best way to halt the ongoing HIV-1 epidemic. However, despite significant efforts to develop a safe and effective... (Review)
Review
An efficacious HIV-1 vaccine is regarded as the best way to halt the ongoing HIV-1 epidemic. However, despite significant efforts to develop a safe and effective vaccine, the modestly protective RV144 trial remains the only efficacy trial to provide some level of protection against HIV-1 acquisition. This review will outline the history of HIV vaccine development, novel technologies being applied to HIV vaccinology and immunogen design, as well as the studies that are ongoing to advance our understanding of vaccine-induced immune correlates of protection.
Topics: AIDS Vaccines; Animals; Antibodies, Neutralizing; Clinical Trials as Topic; Drug Evaluation, Preclinical; HIV Antibodies; HIV Infections; HIV-1; Host-Pathogen Interactions; Humans; Immunogenicity, Vaccine; Outcome Assessment, Health Care; Structure-Activity Relationship; Vaccination; Viral Proteins
PubMed: 29614779
DOI: 10.3390/v10040167 -
Immunological Reviews Jan 2017It is clear that antibodies can play a pivotal role in preventing the transmission of HIV-1 and large efforts to identify an effective antibody-based vaccine to quell... (Review)
Review
It is clear that antibodies can play a pivotal role in preventing the transmission of HIV-1 and large efforts to identify an effective antibody-based vaccine to quell the epidemic. Shortly after HIV-1 was discovered as the cause of AIDS, the search for epitopes recognized by neutralizing antibodies became the driving strategy for an antibody-based vaccine. Neutralization escape variants were discovered shortly thereafter, and, after almost three decades of investigation, it is now known that autologous neutralizing antibody responses and their selection of neutralization resistant HIV-1 variants can lead to broadly neutralizing antibodies in some infected individuals. This observation drives an intensive effort to identify a vaccine to elicit broadly neutralizing antibodies. In contrast, there has been less systematic study of antibody specificities that must rely mainly or exclusively on other protective mechanisms, although non-human primate (NHP) studies as well as the RV144 vaccine trial indicate that non-neutralizing antibodies can contribute to protection. Here we propose a novel strategy to identify new epitope targets recognized by these antibodies for which viral escape is unlikely or impossible.
Topics: AIDS Vaccines; Animals; Antibodies, Neutralizing; Clinical Trials as Topic; Epitopes; HIV Antibodies; HIV Antigens; HIV Infections; HIV-1; Humans; Immune Evasion; Primates
PubMed: 28133809
DOI: 10.1111/imr.12510 -
The New Microbiologica Apr 2022Since the beginning of the HIV/AIDS epidemy in the eighties, hundreds of phase I human immunization studies were performed, however, only nine tested efficacy in phase...
Since the beginning of the HIV/AIDS epidemy in the eighties, hundreds of phase I human immunization studies were performed, however, only nine tested efficacy in phase IIb/III clinical trials. While immunogens for SARS-CoV-2 did move along the development and clinical trial pipeline at unprecedent speed, two HIV immunization vaccine trials, started in 2016 and 2017, did meet non-efficacy criteria at the interim analysis and were thus, halted by the Data and Safety Monitoring Boards. The challenges in the quest to develop a safe, effective and durable HIV vaccine are unchanged. However, as research on HIV vaccine discovery moves forward there are many new tools and platform technologies to iterate vaccine strategies faster. Among these, there is a growing interest to conduct experimental medicine approaches where product development is directly informed by human data at an early stage of product development.
Topics: AIDS Vaccines; Acquired Immunodeficiency Syndrome; COVID-19; HIV Infections; Humans; SARS-CoV-2; Vaccination
PubMed: 35699557
DOI: No ID Found -
Proceedings of the National Academy of... Aug 2014With the 2010s declared the Decade of Vaccines, and Millennium Development Goals 4 and 5 focused on reducing diseases that are potentially vaccine preventable, now is an...
With the 2010s declared the Decade of Vaccines, and Millennium Development Goals 4 and 5 focused on reducing diseases that are potentially vaccine preventable, now is an exciting time for vaccines against poverty, that is, vaccines against diseases that disproportionately affect low- and middle-income countries (LMICs). The Global Burden of Disease Study 2010 has helped better understand which vaccines are most needed. In 2012, US$1.3 billion was spent on research and development for new vaccines for neglected infectious diseases. However, the majority of this went to three diseases: HIV/AIDS, malaria, and tuberculosis, and not neglected diseases. Much of it went to basic research rather than development, with an ongoing decline in funding for product development partnerships. Further investment in vaccines against diarrheal diseases, hepatitis C, and group A Streptococcus could lead to a major health impact in LMICs, along with vaccines to prevent sepsis, particularly among mothers and neonates. The Advanced Market Commitment strategy of the Global Alliance for Vaccines and Immunisation (GAVI) Alliance is helping to implement vaccines against rotavirus and pneumococcus in LMICs, and the roll out of the MenAfriVac meningococcal A vaccine in the African Meningitis Belt represents a paradigm shift in vaccines against poverty: the development of a vaccine primarily targeted at LMICs. Global health vaccine institutes and increasing capacity of vaccine manufacturers in emerging economies are helping drive forward new vaccines for LMICs. Above all, partnership is needed between those developing and manufacturing LMIC vaccines and the scientists, health care professionals, and policy makers in LMICs where such vaccines will be implemented.
Topics: AIDS Vaccines; Communicable Disease Control; Developing Countries; Diarrhea; Global Health; Humans; Malaria Vaccines; Neglected Diseases; Poverty Areas; Respiratory Tract Infections; Tuberculosis Vaccines; Vaccines
PubMed: 25136089
DOI: 10.1073/pnas.1400473111 -
Cell Host & Microbe Mar 2016Development of an effective AIDS vaccine is a global priority. However, the extreme diversity of HIV type 1 (HIV-1), which is a consequence of its propensity to mutate... (Review)
Review
Development of an effective AIDS vaccine is a global priority. However, the extreme diversity of HIV type 1 (HIV-1), which is a consequence of its propensity to mutate to escape immune responses, along with host factors that prevent the elicitation of protective immune responses, continue to hinder vaccine development. Breakthroughs in understanding of the biology of the transmitted virus, the structure and nature of its envelope trimer, vaccine-induced CD8 T cell control in primates, and host control of broadly neutralizing antibody elicitation have given rise to new vaccine strategies. Despite this promise, emerging data from preclinical trials reinforce the need for additional insight into virus-host biology in order to facilitate the development of a successful vaccine.
Topics: AIDS Vaccines; Animals; Antibodies, Neutralizing; CD8-Positive T-Lymphocytes; Drug Discovery; Drug Evaluation, Preclinical; HIV Antibodies; HIV-1; Host-Pathogen Interactions; Primates; Treatment Outcome
PubMed: 26922989
DOI: 10.1016/j.chom.2016.02.002 -
Nature Reviews. Microbiology Nov 2014The ultimate solution to the global HIV-1 epidemic will probably require the development of a safe and effective vaccine. Multiple vaccine platforms have been evaluated... (Review)
Review
The ultimate solution to the global HIV-1 epidemic will probably require the development of a safe and effective vaccine. Multiple vaccine platforms have been evaluated in preclinical and clinical trials, but given the disappointing results of clinical efficacy studies so far, novel vaccine approaches are needed. In this Opinion article, we discuss the scientific basis and clinical potential of novel adenovirus and cytomegalovirus vaccine vectors for HIV-1 as two contrasting but potentially complementary vector approaches. Both of these vector platforms have demonstrated partial protection against stringent simian immunodeficiency virus challenges in rhesus monkeys using different immunological mechanisms.
Topics: AIDS Vaccines; Adenoviridae; Animals; Cytomegalovirus; Disease Models, Animal; Genetic Vectors; HIV Infections; HIV-1; Humans; Macaca mulatta; Simian Immunodeficiency Virus
PubMed: 25296195
DOI: 10.1038/nrmicro3360