Low parasite specific T cell response in clinically immune individuals with low grade Plasmodium falciparum parasitaemia

High-risk human papillomavirus (HPV) infection is the cause of almost all cervical cancers. HPV16 is one of the main risk subtypes. Although screening programs have greatly reduced the prevalence of cervical cancer in developed countries, current diagnostic tests cannot predict if mild lesions may progress into invasive lesions or not. In the current cross-sectional and longitudinal clinical study, we found that the HPV16 E7-specific T cell response in peripheral blood mononuclear cells of HPV16-infected patients is related to HPV16 clearance. It contributes to protecting the squamous interaepithelial lesion (SIL) from further malignant development. Of the HPV16 infected women enrolled (n = 131), 42 had neither intraepithelial lesion nor malignancy (NILM), 33 had low-grade SIL, 39 had high-grade SIL, and 17 had cervical cancer. Only one of 17 (5.9%) cancer patients had a positive HPV16 E7-specific T cell response, dramatically lower than the groups of precancer patients. After one year of follow-up, most women (28/33, 84.8%) with persistent HPV infection did not exhibit a HPV16 E7-specific T cell response. Furthermore, 3 malignantly progressed women, one progressed to high-grade SIL and two progressed to low-grade SIL, were negative to the HPV16 E7-specific T cell response. None of the patients with a positive HPV16 E7-specific T cell response progressed to further deterioration. Our observation suggests that HPV16 E7-specific T cell immunity is significant in viral clearance and contributes in protection against progression to malignancy.

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Immune Response of Humans to the Circumsporozoite Protein of Plasmodium falciparum: Limited T Cell Response to the Immunodominant Central Repeat Region

American Journal of Tropical Medicine and Hygiene ◽

10.4269/ajtmh.1988.39.232 ◽

1988 ◽

Vol 39 (3) ◽

pp. 232-235 ◽

Cited By ~ 8

Author(s):

James R. Campbell ◽

Barry A. Annis ◽

Liliana Kurniawan ◽

Gail Wasserman ◽

Richard Wistar ◽

...

Keyword(s):

Immune Response ◽

Plasmodium Falciparum ◽

T Cell ◽

Cell Response ◽

T Cell Response ◽

Circumsporozoite Protein ◽

Repeat Region

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Epitope Analysis of Human T-Cell Response to MSP-1 of Plasmodium falciparum in Malaria-Nonexposed Individuals

International Archives of Allergy and Immunology ◽

10.1159/000237637 ◽

1997 ◽

Vol 114 (1) ◽

pp. 15-22 ◽

Cited By ~ 7

Author(s):

Nobuo Ohta ◽

Kimiko Iwaki ◽

Makoto Itoh ◽

Jun Fu ◽

Shigeko Nakashima ◽

...

Keyword(s):

Plasmodium Falciparum ◽

T Cell ◽

Cell Response ◽

T Cell Response ◽

Epitope Analysis ◽

Human T Cell

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The Th1 Immune Response to Plasmodium falciparum Circumsporozoite Protein Is Boosted by Adenovirus Vectors 35 and 26 with a Homologous Insert

Clinical and Vaccine Immunology ◽

10.1128/cvi.00311-10 ◽

2010 ◽

Vol 17 (11) ◽

pp. 1687-1694 ◽

Cited By ~ 41

Author(s):

Katarina Radošević ◽

Ariane Rodriguez ◽

Angelique A. C. Lemckert ◽

Marjolein van der Meer ◽

Gert Gillissen ◽

...

Keyword(s):

Immune Response ◽

Plasmodium Falciparum ◽

T Cell ◽

Cell Response ◽

T Cell Responses ◽

T Cell Response ◽

Virus Surface ◽

Cell Responses ◽

Ifn Γ ◽

Th1 Immune Response

ABSTRACT The most advanced malaria vaccine, RTS,S, is comprised of an adjuvant portion of the Plasmodium falciparum circumsporozoite (CS) protein fused to and admixed with the hepatitis B virus surface antigen. This vaccine confers short-term protection against malaria infection, with an efficacy of about 50%, and induces particularly B-cell and CD4+ T-cell responses. In the present study, we tested by the hypothesis that the Th1 immune response to CS protein, in particular the CD8+ T-cell response, which is needed for strong and lasting malaria immunity, is boosted to sustainable levels vectors adenovirus and 26 with an homologous insert 35 (Ad35.CS/Ad26.CS). In this study, we evaluated immune responses induced with vaccination regimens based on an adjuvant-containing, yeast-produced complete CS protein followed by two recombinant low-seroprevalence adenoviruses expressing P. falciparum CS antigen, Ad35.CS (subgroup B) and Ad26.CS (subgroup D). Our results show that (i) the yeast (Hansenula polymorpha)produced, adjuvanted full-length CS protein is highly potent in inducing high CS-specific humoral responses in mice but produces poor T-cell responses, (ii) the Ad35.CS vector boosts the gamma interferon-positive (IFN-γ+) CD8+ T-cell response induced by the CS protein immunization and shifts the immune response toward the Th1 type, and (iii) a three-component heterologous vaccination comprised of a CS protein prime followed by boosts with Ad35.CS and Ad26.CS elicits an even more robust and sustainable IFN-γ+ CD8+ T-cell response than one- or two-component regimens. The Ad35.CS/Ad26.CS combination boosted particularly the IFN-γ+ and tumor necrosis factor alpha-positive (TNF-α+) T cells, confirming the shift of the immune response from the Th2 type to the Th1 type. These results support the notion of first immunizations of infants with an adjuvanted CS protein vaccine, followed by a booster Ad35.CS/Ad26.CS vaccine at a later age, to induce lasting protection against malaria for which the Th1 response and immune memory is required.

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CTIM-24. RANDOMIZED TRIAL OF NEOADJUVANT VACCINATION WITH TUMOR-CELL LYSATE INDUCES T CELL RESPONSE IN LOW-GRADE GLIOMAS

Neuro-Oncology ◽

10.1093/neuonc/noab196.216 ◽

2021 ◽

Vol 23 (Supplement_6) ◽

pp. vi55-vi55

Author(s):

Jennie Taylor ◽

Hirokazu Ogino ◽

Takahide Nejo ◽

David Gibson ◽

Payal Watchmaker ◽

...

Keyword(s):

T Cell ◽

Peripheral Blood ◽

Cell Response ◽

Cd8 T Cell ◽

Additional Treatment ◽

T Cell Response ◽

Low Grade ◽

Who Grade ◽

Slow Growth Rate ◽

Low Grade Gliomas

Abstract BACKGROUND The prognosis of WHO grade II low-grade gliomas (LGG) is varied with potential for long survival.Given their relatively intact immune system and slow growth rate, vaccines are an attractive treatment strategy for LGG in an attempt to defer more toxic treatments. The goals of this pilot study were to evaluate safety and immunological effects of vaccination with GBM6-AD, an allogeneic glioblastoma stem cell line lysate, with poly-ICLC in LGG. METHODS Eligible patients were ≥ 18 years old, ≥ 70 KPS, with recurrent LGG or imaging consistent with LGG, and amenable to resection. Patients were randomized to vaccine prior to surgery (Arm 1) or not (Arm 2) and all received adjuvant vaccine. Co-primary outcomes were safety and immune response in the tumor, with exploratory outcomes of survival and immunologic effects in peripheral blood. RESULTS A total of 17 eligible patients were evaluable – nine into Arm 1 and eight into Arm 2. Median age was 33 years, with median time from initial diagnosis of 4.7 years (0 – 20). Two patients (11.8%) previously received radiotherapy and seven (41.2%) prior systemic therapy. No dose limiting toxicities or grade 3 AEs were observed. Neoadjuvant vaccination induced up regulation of type-1 cytokines and chemokines in peripheral blood, and CD8+ T cell clones that reacted to the vaccine were also detected in the tumor. Median follow-up time from first post-operative vaccine was 20.8 months with median PFS of 11.0 months and time to change in therapy of 23.7 months. Of the six patients to receive additional treatment, three had second surgery only one confirming malignant progression to anaplastic oligodendroglioma. CONCLUSION Treatment was well-tolerated with no regimen-limiting toxicity. GBM6-AD plus poly-ICLC induced effector CD8+ T cell response in peripheral blood and enables some vaccine-reactive CD8+ T cells to migrate into the TME. Further investigation is warranted.

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