Lipopeptide vaccines—yesterday, today, and tomorrow

BenMohamed, Lbachir; Wechsler, Steven L.; Nesburn, Anthony B.

doi:10.1016/s1473-3099(02)00318-3

Cited by 170 publications

(202 citation statements)

References 60 publications

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“…The lipopeptide technology has shown its strength in recent years by providing much needed immunogens for the safe and efficient induction of CD8 + Tcells (reviewed in [5,6]). We have recently shown that synthetic epitopebased vaccines incorporating the lipid moiety S-[2,3-bis(palmitoyloxy)propyl]cysteine, (Pam2Cys), which corresponds to the lipid component of macrophageactivating lipopeptide 2 (MALP-2) from Mycoplasma fermentans [7], are efficacious in the clearance of viral, bacterial and tumour agents in mouse models of infection anddisease [8].Their mode ofactionappearstorelyonthe ability of the lipid to interact with Toll-like receptor 2 (TLR2) on DC, which triggers DC maturation resulting in an increased efficiency of presentation of the peptide epitopes [8].…”

Section: Induction Of Cd8mentioning

confidence: 99%

Intranasal lipopeptide primes lung‐resident memory CD8⁺ T cells for long‐term pulmonary protection against influenza

et al. 2006

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The longevity of the influenza virus-specific CD8 + T cell response following intranasal delivery of a synthetic lipopeptide was investigated and the characteristics and location of the cells associated with viral clearance examined. The lipopeptide, incorporating an epitope for CD8 + T cells and another for CD4 + T cells with the lipid moiety S-[2,3-bis(palmitoyloxy)propyl]cysteine (Pam2Cys) attached, induced potent and long-lived pulmonary protection. Both the lipopeptide and its largely unprotective non-lipidated counterpart elicited comparable numbers of CD8 + T cells in the spleen, which was the main location of the memory pool. However, the lipopeptide, unlike the non-lipidated peptide, also induced a substantial memory population that remained in the lungs and was rapidly activated upon viral challenge months later. These lipopeptide-induced lung-resident CD8 + T cells were also very similar in number and IFN-c-secreting potential to those induced by prior exposure to the virus itself and are likely mediators of initial viral clearance prior to recruitment from the expanding lymph node T cell pool. Significant clearing responses were demonstrated as late as 9 months post-lipopeptide vaccination. This study shows that CD8 + T cells primed by the lipopeptide are not only long-lived but can take up residence in the lung where they are important early mediators of pulmonary protection.

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Section: Induction Of Cd8mentioning

confidence: 99%

Intranasal lipopeptide primes lung‐resident memory CD8⁺ T cells for long‐term pulmonary protection against influenza

et al. 2006

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“…The median count at treatment interruption for patients who remained off therapy was 412 (IQR, 299 to 832)/mm 3 at W96. Only 4 of the 21 assessable patients had a nadir CD4 ϩ T-cell count above 350 cells/mm 3 , and 5 of the 8 patients who remained off therapy at 96 weeks had a CD4 ϩ T-cell nadir of between 200 and 250/mm 3 .…”

Section: Characteristics Of Patientsmentioning

confidence: 99%

“…Eight patients were still off HAART at 96 weeks, with a median pVL of 4 (IQR, 1.7 to 4.6) log 10 copies/ml and a median CD4 ϩ T-cell count of 412 (IQR, 299 to 832)/mm 3 . Interestingly, one of these eight patients had an undetectable pVL (Ͻ50 copies/ml) at W96 ( Table 2; Fig.…”

Section: Characteristics Of Patientsmentioning

confidence: 99%

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Immunological Responses and Long-Term Treatment Interruption after Human Immunodeficiency Virus Type 1 (HIV-1) Lipopeptide Immunization of HIV-1-Infected Patients: the LIPTHERA Study

Pialoux

Quercia

Gahéry

et al. 2008

Clin Vaccine Immunol

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We studied the time course of immunological and virological markers after highly active antiretroviral therapy (HAART) interruption in chronically human immunodeficiency virus type 1 (HIV-1)-infected patients immunized with an HIV lipopeptide preparation. In a prospective open pilot study, 24 HIV-1-infected HAARTtreated patients with undetectable plasma viral loads (pVLs) and CD4 ؉ T-cell counts above 350/mm 3 were immunized at weeks 0, 3, and 6 with a candidate vaccine consisting of six HIV lipopeptides. At week 24, patients with pVLs of <1.7 log 10 copies/ml were invited to stop taking HAART. Antiretroviral therapy was resumed if the pVL rose above 4.47 log 10 copies/ml and/or if the CD4 ؉ cell count fell below 250/mm 3 . Immunological and virologic parameters were studied before and after HAART interruption. The median baseline and nadir CD4 ؉ cell counts were 482 (interquartile range [IQR], 195 to 826) and 313 (IQR, 1 to 481)/mm 3 , respectively. New specific CD8 ؉ cell responses to HIV-1 epitopes were detected after immunization in 13 (57%) of 23 assessable patients. Twenty-one patients were evaluated 96 weeks after HAART interruption. The median time to pVL rebound was 4 weeks (IQR, 2 to 6), and the median peak pVL was 4.26 (IQR, 3 to 5) log 10 copies/ml. Thirteen of these 21 patients resumed HAART a median of 60 weeks after immunization (IQR, 9.2 to 68.4 weeks), when the median pVL was 4.8 (IQR, 2.9 to 5.7) log 10 copies/ml and the median CD4 ؉ cell count was 551 (IQR, 156 to 778)/mm 3 . Eight patients were still off therapy at 96 weeks, with a median pVL of 4 (IQR, 1.7 to 4.6) log 10 copies/ml and a median CD4 ؉ cell count of 412 (IQR, 299 to 832)/mm 3 . No clinical disease progression had occurred. Despite the lack of a control arm, these findings warrant a randomized study of therapeutic vaccination with HIV lipopeptides followed by long-term HAART interruption in AIDS-free chronically infected patients.Highly active antiretroviral therapy (HAART) limits human immunodeficiency virus type 1 (HIV-1) replication and drastically reduces AIDS-related morbidity and mortality (35). However, HAART is not universally available, must be taken for life, and has clinical and/or metabolic adverse effects in 40 to 60% of patients.Long-term HAART increases the number of naive immune T cells and improves the functional status of CD4 ϩ and CD8 ϩ

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“…CTL-based immunotherapy is based on the concept that HBV-specific CTLs control infection by suppressing HBV replication in infected humans [51] . Vitiello et al [52] developed a lipopeptide-based vaccine containing one CTL epitope from the HBV core region.…”

Section: Ctl-based Therapymentioning

confidence: 99%

Novel approaches towards conquering hepatitis B virus infection

Wu¹

2007

WJG

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Currently approved treatments for hepatitis B virus (HBV) infection include the immunomodulatory agent, IFN-α, and nucleos(t)ide analogues. Their efficacy is limited by their side effects, as well as the induction of viral mutations that render them less potent. It is thus necessary to develop drugs that target additional viral antigens. Chemicals and biomaterials by unique methods of preventing HBV replication are currently being developed, including novel nucleosides and newly synthesized compounds such as capsid assembling and mRNA transcription inhibitors. Molecular therapies that target different stages of the HBV life cycle will aid current methods to manage chronic hepatitis B (CHB) infection. The use of immunomodulators and gene therapy are also under consideration. This report summarizes the most recent treatment possibilities for CHB infection. Emerging therapies and their potential mechanisms, efficacy, and pitfalls are discussed.

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Lipopeptide vaccines—yesterday, today, and tomorrow

Cited by 170 publications

References 60 publications

Intranasal lipopeptide primes lung‐resident memory CD8⁺ T cells for long‐term pulmonary protection against influenza

Intranasal lipopeptide primes lung‐resident memory CD8⁺ T cells for long‐term pulmonary protection against influenza

Immunological Responses and Long-Term Treatment Interruption after Human Immunodeficiency Virus Type 1 (HIV-1) Lipopeptide Immunization of HIV-1-Infected Patients: the LIPTHERA Study

Novel approaches towards conquering hepatitis B virus infection

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Lipopeptide vaccines—yesterday, today, and tomorrow

Cited by 170 publications

References 60 publications

Intranasal lipopeptide primes lung‐resident memory CD8+ T cells for long‐term pulmonary protection against influenza

Intranasal lipopeptide primes lung‐resident memory CD8+ T cells for long‐term pulmonary protection against influenza

Immunological Responses and Long-Term Treatment Interruption after Human Immunodeficiency Virus Type 1 (HIV-1) Lipopeptide Immunization of HIV-1-Infected Patients: the LIPTHERA Study

Novel approaches towards conquering hepatitis B virus infection

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Product

Resources

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Intranasal lipopeptide primes lung‐resident memory CD8⁺ T cells for long‐term pulmonary protection against influenza

Intranasal lipopeptide primes lung‐resident memory CD8⁺ T cells for long‐term pulmonary protection against influenza