Unusual antigen presentation offers new insight into HIV vaccine design

McMichael, Andrew J.; Picker, Louis J.

doi:10.1016/j.coi.2017.04.009

Cited by 12 publications

(7 citation statements)

References 36 publications

(57 reference statements)

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“…Overall, vaccine-induced CD8 + T cells prevented (most probably by contact) activation of SIV-RNA-infected CD4 + T cells, which in turn prevented the reverse transcription of SIV RNA into SIV DNA (which is activation dependent) and the subsequent cascade of events ending in virus replication and release. These findings are in keeping with the potential protective role of MHC-E observed in HIV-infected individuals [49].…”

Section: Ex Vivo Functional Characteristics Of Vaccine-induced Tolerogenic Cd8 + T-regssupporting

confidence: 87%

Evidence of a tolerogenic vaccine against AIDS in the Chinese macaque prefigures a potential human vaccine

Andrieu

Lü

2021

Arch Virol

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In 2006 we discovered a new type of mucosal vaccine against simian immunodeficiency virus (SIV) in Chinese macaques. Here, we review 15 years of our published work on this vaccine, which consists of inactivated SIVmac239 particles adjuvanted with Bacillus Calmette-Guérin, Lactobacillus plantarum, or Lactobacillus rhamnosus. Without adjuvant, the vaccine administered by the intragastric route induced the usual SIV-specific humoral and cellular immune responses but provided no protection against intrarectal challenge with SIVmac239. In contrast, out of 24 macaques immunized with the adjuvanted vaccine and challenged intrarectally with SIVmac239 or SIVB670, 23 were sterilely protected for up to five years, while all control macaques were infected. This protection was confirmed by an independent group from the Pasteur Institute. During the past 15 years, we have identified the mechanism of action of the vaccine and discovered that the vaccinated macaques produced a previously unrecognized class of MHC-Ib/E-restricted CD8+ T cells (which we refer to as tolerogenic CD8+ T cells) that suppressed the activation of SIV-RNA-infected CD4+ T cells and thereby inhibited the (activation-dependent) reverse transcription of the virus, which in turn prevented the establishment of SIV infection. Importantly, we discovered also that the tolerogenic CD8+ T cell subset observed in vaccinated Chinese macaques could also be found in human elite controllers, a small group of HIV-infected patients in whom these tolerogenic CD8+ T cells were shown to naturally suppress viral replication. Given that SIV and HIV require activated immune cells in which to replicate, the specific prevention of activation of SIV-RNA-containing CD4+ T cells by a tolerogenic vaccine approach offers an exciting new avenue in HIV vaccine research.

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Section: Ex Vivo Functional Characteristics Of Vaccine-induced Tolerogenic Cd8 + T-regssupporting

confidence: 87%

Evidence of a tolerogenic vaccine against AIDS in the Chinese macaque prefigures a potential human vaccine

Andrieu

Lü

2021

Arch Virol

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“…Additionally, current findings show that the use of rhesus monkey cytomegalovirus (RhCMV)-based simian immunodeficiency virus (SIV) vaccine can directly prime major histocompatibility complex class-E (MHC-E)-restricted CD8 + T-cell responses. The unusual pathway of this antigen presentation can possibly extend the success of HIV vaccine in the future [ 87 ]. Adoptive T-cell transfer and immunotherapy have limitations on cell transfusion and take a longer period of time to modify and expand cells.…”

Section: Discussionmentioning

confidence: 99%

Current Peptide and Protein Candidates Challenging HIV Therapy beyond the Vaccine Era

Chupradit

Moonmuang

Nangola

et al. 2017

Viruses

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Human immunodeficiency virus (HIV) is a causative agent of acquired immune deficiency syndrome (AIDS). Highly active antiretroviral therapy (HAART) can slow down the replication of HIV-1, leading to an improvement in the survival of HIV-1-infected patients. However, drug toxicities and poor drug administration has led to the emergence of a drug-resistant strain. HIV-1 immunotherapy has been continuously developed, but antibody therapy and HIV vaccines take time to improve its efficiency and have limitations. HIV-1-specific chimeric antigen receptor (CAR)-based immunotherapy founded on neutralizing antibodies is now being developed. In HIV-1 therapy, anti-HIV chimeric antigen receptors showed promising data in the suppression of HIV-1 replication; however, autologous transfusion is still a problem. This has led to the development of effective peptides and proteins for an alternative HIV-1 treatment. In this paper, we provide a comprehensive review of potent anti-HIV-1 peptides and proteins that reveal promising therapeutic activities. The inhibitory mechanisms of each therapeutic molecule in the different stages of the HIV-1 life cycle will be discussed herein.

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“…Their varying amino acid length implies that HLA-E has higher peptide binding plasticity than solely the VL9 peptide [75]. These non-canonical T cells contribute to the majority of T cells present during active Mtb infection [77], and overshadow T cells restricted by canonical HLA class Ia epitope presentation [78,79]. Mtb antigens presented by HLA-E to CD8 + T cells can induce either a cytotoxic or regulatory phenotype, consequently inhibiting Mtb pathogenesis and growth in infected macrophages [7,78].…”

Section: Mycobacterium Tuberculosismentioning

confidence: 99%

HLA-E: exploiting pathogen-host interactions for vaccine development

Sharpe

Bowyer

Brackenridge

et al. 2019

Clinical and Experimental Immunology

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Summary Viruses, when used as vectors for vaccine antigen delivery, can induce strong cellular and humoral responses against target epitopes. Recent work by Hansen et al. describes the use of a cytomegalovirus‐vectored vaccine, which is able to generate a stable effector‐memory T cell population at the sites of vaccination in rhesus macaques. This vaccine, targeted towards multiple epitopes in simian immunodeficiency virus (SIV), did not induce classical CD8+ T cells. However, non‐canonical CD8+ T cell induction occurred via major histocompatibility complex (MHC) class II and MHC‐E. The MHC‐E‐restricted T cells could recognize broad epitopes across the SIV peptides, and conferred protection against viral challenge to 55% of vaccinated macaques. The human homologue, human leucocyte antigen (HLA)‐E, is now being targeted as a new avenue for vaccine development. In humans, HLA‐E is an unusually oligomorphic class Ib MHC molecule, in comparison to highly polymorphic MHC class Ia. Whereas MHC class Ia presents peptides derived from pathogens to T cells, HLA‐E classically binds defined leader peptides from class Ia MHC peptides and down‐regulates NK cell cytolytic activity when presented on the cell surface. HLA‐E can also restrict non‐canonical CD8+ T cells during natural infection with various pathogens, although the extent to which they are involved in pathogen control is mostly unknown. In this review, an overview is provided of HLA‐E and its ability to interact with NK cells and non‐canonical T cells. Also discussed are the unforeseen beneficial effects of vaccination, including trained immunity of NK cells from bacille Calmette–Guérin (BCG) vaccination, and the broad restriction of non‐canonical CD8+ T cells by cytomegalovirus (CMV)‐vectored vaccines in pre‐clinical trials.

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Unusual antigen presentation offers new insight into HIV vaccine design

Cited by 12 publications

References 36 publications

Evidence of a tolerogenic vaccine against AIDS in the Chinese macaque prefigures a potential human vaccine

Evidence of a tolerogenic vaccine against AIDS in the Chinese macaque prefigures a potential human vaccine

Current Peptide and Protein Candidates Challenging HIV Therapy beyond the Vaccine Era

HLA-E: exploiting pathogen-host interactions for vaccine development

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