Combinatorial Herpes Simplex Vaccine Strategies: From Bedside to Bench and Back

Chentoufi, Aziz Alami; Dhanushkodi, Nisha R; Srivastava, Ruchi; Prakash, Swayam; Coulon, Pierre-Gregoire A; Zayou, Latifa; Vahed, Hawa; Chentoufi, Hiba A.; Hormi–Carver, Kathy; BenMohamed, Lbachir

doi:10.3389/fimmu.2022.849515

Cited by 19 publications

(13 citation statements)

References 140 publications

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“…HPV can infect the stratified squamous epithelium and stimulate cellular proliferation, resulting in benign hyperplasia or in some cases, cervical cancer following prolonged, unresolved infection ( Szymonowicz and Chen, 2020 ; Alimena et al., 2022 ). HSV-2 can produce genital herpes in the form of painful sores at the site of viral replication and shedding and has the capacity to penetrate the central nervous system and induce latent dorsal root ganglia infection when in touch with the genital mucosal surface ( Chentoufi et al., 2022 ). Because each of these illnesses raises the chance of developing another STI, the epidemiology of these infections is exceedingly convoluted ( Torcia, 2019 ).…”

Section: Probiotic Lactobacilli In the Treatment Of Vaginal Infectionsmentioning

confidence: 99%

Use of probiotic lactobacilli in the treatment of vaginal infections: In vitro and in vivo investigations

Liu

et al. 2023

Front. Cell. Infect. Microbiol.

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The vaginal microbiome is a distinct component of the human microbiome that is colonized by a wide variety of microorganisms. Lactobacilli are the most frequently identified microorganisms in the healthy human vagina. These Gram-positive bacilli can acidify the vaginal microenvironment, inhibit the proliferation of other pathogenic microorganisms, and promote the maintenance of a eubiotic vaginal microbiome. However, a vaginal flora with a reduced proportion or abundance of lactobacilli is associated with various vaginal infections that have been linked to serious health consequences such as infertility, preterm birth, pelvic inflammatory disease, premature rupture of membranes, and miscarriage. Due to their “Generally Recognized as Safe” classification and critical role in vaginal health, probiotic lactobacilli have been widely used as an alternative or adjunct to traditional antibiotic therapy for the treatment of vaginal infections and restoration of the vaginal microbiome. This review focuses on the significant role of probiotic lactobacilli in the vaginal microenvironment and discusses the use of probiotic lactobacilli in the treatment of female vaginal infections in vitro and in vivo.

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Section: Probiotic Lactobacilli In the Treatment Of Vaginal Infectionsmentioning

confidence: 99%

Use of probiotic lactobacilli in the treatment of vaginal infections: In vitro and in vivo investigations

Liu

et al. 2023

Front. Cell. Infect. Microbiol.

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“…Madmoodpoor et al also outlined a higher expression of PD-1 in circulating lymphocytes of patients with severe COVID-19 compared with healthy controls (8). Recurrent or latent infections by many pathogens as well as several vaccines in development have shown to induce overexpression of these IC molecules, and thus exhaustion in immune cells, leading to increases in inhibitory IC signals and immune evasion (29)(30)(31). As a consequence of increased inhibitory IC receptors, T cells are exhausted, leading to viral escape from immune control (32).…”

Section: Discussionmentioning

confidence: 99%

Evidence of exhausted lymphocytes after the third anti-SARS-CoV-2 vaccine dose in cancer patients

et al. 2022

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IntroductionEvidence is scant regarding the long-term humoral and cellular responses Q7 triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines in cancer patients after repeated booster doses. The possibility of T-cell exhaustion following these booster doses in this population has not yet been fully studied and remains uncertain.MethodsIn this single-center prospective observational study, we explored the specific humoral and cellular response to S1 antigen in 36 patients with solid malignancies at baseline, and after the second and third doses of the mRNA-1273 vaccine.ResultsA dual behavior was observed: 24 (66.7%) patients showed partial specific IFN-γ response after the second dose that was further enhanced after the third dose; and 11 (30.5%) already showed an optimal response after the second dose and experienced a marked fall-off of specific IFN-γ production after the third (4 patients negativization), which might suggest T cell exhaustion due to repetitive priming to the same antigen. One (2.8%) patient had persistently negative responses after all three doses. Seroconversion occurred in all patients after the second dose. We then studied circulating exhausted CD8+ T-cells in 4 patients from each of the two response patterns, those with increase and those with decrease in cellular response after the third booster. The patients with decreased cellular response after the booster had a higher expression of PD1+CD8+ and CD57+PD1+CD8+ exhausted T cells compared with those with an increased cellular response both in vivo and in vitro. The proportion of PD1+CD8+ and CD57+PD1+CD8+ exhausted T cells inversely correlated with IFN-γ production.DiscussionOur preliminary data show that the two-dose SARS-CoV-2 vaccine regimen was beneficial in all cancer patients of our study. An additional booster seems to be beneficial in suboptimal vaccine seroconverters, in contrast to maximal responders that might develop exhaustion. Our data should be interpreted with caution given the small sample size and highlight the urgent need to validate our results in other independent and larger cohorts. Altogether, our data support the relevance of immunological functional studies to personalize preventive and treatment decisions in cancer patients.

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“…T cell exhaustion is a dysfunctional state of T cells characterized by the high expression level of immune-checkpoint (IC) receptors, such as PD-1, decreased proliferation and production of cytotoxic cytokines, and altered transcriptional and metabolic pro les (23). Recurrent or latent infections by many pathogens as well as several vaccines in development have shown to induce overexpression of these IC molecules, and thus exhaustion in immune cells, leading to increases in inhibitory IC signals and immune evasion (24)(25)(26). As a consequence of increased inhibitory IC receptors, T cells are exhausted, leading to viral escape from immune control (27).…”

Section: Discussionmentioning

confidence: 99%

Evidence of Exhausted Lymphocytes after the Third anti-SARS-CoV-2 Vaccine Dose in Cancer Patients

Fuentes

Mohamed

Aguilar

et al. 2022

Preprint

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Evidence is scant regarding the long-term humoral and cellular responses triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines in cancer patients after repeated booster doses. The possibility of T-cell exhaustion following these booster doses in this population has not yet been fully studied and remains uncertain. In this observational study, we explored the specific humoral and cellular response to S1 antigen in 36 patients with solid malignancies at baseline, and after the second and third doses of the mRNA-1273 vaccine. A dual behavior was observed: 24 (66.7%) patients showed partial specific IFN-γ response after the second dose that was further enhanced after the third dose; and 11 (30.5%) already showed an optimal response after the second dose and experienced a marked fall-off of specific IFN-γ production after the third (4 patients negativization), which might suggest T cell exhaustion due to repetitive priming to the same antigen. One (2.8%) patient had persistently negative responses after all three doses. Seroconversion occurred in all patients after the second dose. We then studied circulating exhausted CD8 + T-cells in 4 patients from each of the two response patterns, those with increase and those with decrease in cellular response after the third booster. The patients with decreased cellular response after the booster had a higher expression of CD57hiPD1hiCD8+ and CD57intPD1hiCD8+ exhausted T cells compared with those with an increased cellular response both in vivo and in vitro. Our preliminary data show that the two-dose SARS-CoV-2 vaccine regimen was beneficial in all cancer patients. An additional booster seems to be beneficial in non-optimal cancer responders to SARS-CoV-2 vaccines, in contrast to maximal responders that might develop exhaustion. Our data should be interpreted with caution given the small sample size and highlight the urgent need to validate our results in other independent and larger cohorts. Altogether, our data support the relevance of immunological functional studies to personalize preventive and treatment decisions in cancer patients.

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Combinatorial Herpes Simplex Vaccine Strategies: From Bedside to Bench and Back

Cited by 19 publications

References 140 publications

Use of probiotic lactobacilli in the treatment of vaginal infections: In vitro and in vivo investigations

Use of probiotic lactobacilli in the treatment of vaginal infections: In vitro and in vivo investigations

Evidence of exhausted lymphocytes after the third anti-SARS-CoV-2 vaccine dose in cancer patients

Evidence of Exhausted Lymphocytes after the Third anti-SARS-CoV-2 Vaccine Dose in Cancer Patients

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