Immunogenicity, Immune Dynamics, and Subsequent Response to the Booster Dose of Heterologous versus Homologous Prime-Boost Regimens with Adenoviral Vector and mRNA SARS-CoV-2 Vaccine among Liver Transplant Recipients: A Prospective Study

BACKGROUND: Heterologous prime-boost vaccination potentially augments the immune response against SARS-CoV-2 in liver transplant (LT) recipients. We investigated immunogenicity induced by different primary prime-boost vaccination protocols and the subsequent response to the booster vaccine among LT recipients. METHODS: LT recipients, who received primary immunisation with ChAdOx1/ChAdOx1 or ChAdOx1/BNT162b2, were administered the third dose of mRNA-1273 three months following the primary vaccination. Blood samples were collected before and after primary vaccination and post-booster. The levels of receptor binding domain antibody (anti-RBD) and neutralising antibody (sVNT) and spike-specific T-cell responses were assessed. RESULTS: Among the 89 LT recipients, patients receiving ChAdOx1/BNT162b2 had significantly higher anti-RBD titres, sVNT, and cellular response after primary vaccination than those receiving ChAdOx1/ChAdOx1 (p 90% of LT patients, with only 12.3% positive against the Omicron variant. CONCLUSIONS: ChAdOx1/BNT162b2 evoked a significantly higher immunological response than ChAdOx1/ChAdOx1 in LT recipients. The booster strategy substantially induced robust immunity against wild type in most patients but was less effective against the Omicron strain

A Novel Immunodominant CD8+ T Cell Response Restricted by a Common HLA-C Allele Targets a Conserved Region of Gag HIV-1 Clade CRF01_AE Infected Thais

Background: CD8+ T cell responses play an important role in the control of HIV-1. The extensive sequence diversity of HIV-1 represents a critical hurdle to developing an effective HIV-1 vaccine, and it is likely that regional-specific vaccine strains will be required to overcome the diversity of the different HIV-1 clades distributed world-wide. Unfortunately, little is known about the CD8+ T cell responses against CRF01_AE, which is responsible for the majority of infections in Southeast Asia. Methodology/Principal Findings: To identify dominant CD8+ T cell responses recognized in HIV-1 clade CRF01_AE infected subjects we drew upon data from an immunological screen of 100 HIV-1 clade CRF01_AE infected subjects using IFN-gamma ELISpot to characterize a novel immunodominant CD8+ T cell response in HIV-1 Gag restricted by HLA-Cw*0102 (p24, 277YSPVSILDI 285, YI9). Over 75% of Cw*0102+ve subjects targeted this epitope, representing the strongest response in more than a third of these individuals. This novel CD8 epitope was located in a highly conserved region of HIV-1 Gag known to contain immunodominant CD8 epitopes, which are restricted by HLA-B*57 and -B*27 in clade B infection. Nonetheless, viral escape in this epitope was frequently observed in Cw*0102+ve subjects, suggestive of strong selection pressure being exerted by this common CD8+ T cell response. Conclusions/Significance: As HLA-Cw*0102 is frequently expressed in the Thai population (allelic frequency of 16.8%), this immunodominant Cw*0102-restricted Gag epitope may represent an attractive candidate for vaccines specific to CRF01_AE and may help facilitate further studies of immunopathogenesis in this understudied HIV-1 clade. © 2011 Buranapraditkun et al

The role of CTL in the natural history of HIV infection

SIGLEAvailable from British Library Document Supply Centre- DSC:DN056702 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

HIV-1 Replication in HIV-Infected Individuals Is Significantly Reduced When Peripheral Blood Mononuclear Cells Are Superinfected with HSV-1

Herpes simplex virus (HSV) can cause generalized infection in human immunodeficiency virus- (HIV-) infected patients leading to death. This study investigated HSV-1 replication in PBMCs from 25 HIV-infected individuals and 15 healthy donors and the effects of HSV-1 superinfection on HIV-1 production. Herpes viral entry mediator (HVEM) receptor on T lymphocytes was also evaluated. Our results confirmed that the number of activated (CD3+ and CD38+) T lymphocytes in HIV-infected individuals (46.51±17.54%) was significantly higher than in healthy donors (27.54±14.12%, P value = 0.001) without any significant differences in HVEM expression. Even though the percentages of HSV-1 infected T lymphocytes between HIV-infected individuals (79.25±14.63%) and healthy donors (80.76±7.13%) were not different (P value = 0.922), yet HSV-1 production in HIV-infected individuals (47.34±11.14×103 PFU/ml) was significantly greater than that of healthy donors (34.17±8.48×103 PFU/ml, P value = 0.001). Moreover, HSV-1 virions were released extracellularly rather than being associated with the cells, and superinfection of HSV-1 at a multiplicity of infection (MOI) of 5 significantly decreased HIV production (P value < 0.001)

Mouse acquired HPV tumor using dorsal skin-fold window chamber

327-332Human papillomavirus (HPV) plays important role in developing several types of cancer especially cervical cancer. In order to understand the viral pathogenesis, the animal model of HPV infection is very necessary. This communication reports establishment of an animal model carrying implanted HeLa cells, a human cervical cancer cell line via dorsal skin-fold window chambers. Nude mice were divided into 4 groups; each group contained different amount of HeLa cells, 2.5×105, 5×105, and 1×106 cells, and cell free medium (control), respectively. The results showed that even using the low number of HeLa cells (2.5×105), the tumor microvasculature was developed at 2 weeks after implantation with the enlarged tumor margin which then progressed to tumor mass in the following week. The existing tumor was confirmed to be HeLa-cell type by PCR, in situ hybridization, and HPV genotyping. By using linear regression analysis, it indicated that means of tumor size from each group significantly increased in relation to number of HeLa cells used (R2 = 0.98, y = 0.1171x+4.35). This mouse model will be useful for the further HPV studies particularly anti-cancer drugs efficacy

Cytotoxic function of gamma delta (<img src='/image/spc_char/gamma2.gif' border=0>/<img src='/image/spc_char/delta1.gif' border=0>) T cells against pamidronate- treated cervical cancer cells </span></span>

597-605The cytotoxic function of polyclonal expanded / T cells against pamidronate-treated cervical cancer cells in vitro and in vivo were determined. The / T cells were isolated and purified from PBMCs by using miniMACS and were later treated with 10 μM pamidronate. The expansion of / T cells was 15 times more than the non-stimulated cells. Among the expanded / T cells, 47% were V9/V2 T cells with a purity of 87%. Analyzing the cytotoxic function of / T cells against 3 cervical cancer cells in vitro by LDH cytotoxicity test revealed that the killing efficacy increased if the cervical cancer cells (HeLa, SiHa and CaSki) were pretreated with pamidronate. The presence of CD107 on / T cells indicated the degranulation of perforin and granzyme pathway is one of the mechanisms used by the / T cells to kill cancer cells. The killing ability of / T cells against cancer cells in vivo was preliminary assessed by using mouse baring HeLa cells. The results demonstrated that / T cells induce apoptosis in tumor cells. Our study supports the usefulness of / T cells in future development of immunotherapy for cervical cancer. </span

Clinical outcome of HIV viraemic controllers and noncontrollers with normal CD4 counts is exclusively determined by antigen-specific CD8+ T-cell-mediated HIV suppression.

In this cross-sectional study we evaluated T-cell responses using several assays to determine immune correlates of HIV control that distinguish untreated viraemic controllers (VC) from noncontrollers (NC) with similar CD4 counts. Samples were taken from 65 ART-naïve chronically HIV-infected VC and NC from Thailand with matching CD4 counts in the normal range (>450 cells/μl). We determined HIVp24-specific T-cell responses using standard Interferon-gamma (IFNγ) ELISpot assays, and compared the functional quality of HIVp24-specific CD8+ T-cell responses using polychromatic flow cytometry. Finally, in vitro HIV suppression assays were performed to evaluate directly the activity of CD8+ T cells in HIV control. Autologous CD4+ T cells were infected with primary patient-derived HIV isolates and the HIV suppressive activity of CD8+ T cells was determined after co-culture, measuring production of HIVp24 Ag by ELISA. The HIVp24-specific T-cell responses of VC and NC could not completely be differentiated through measurement of IFNγ-producing cells using ELISpot assays, nor by the absolute cell numbers of polyfunctional HIVp24-specific CD8+ T cells. However, in vitro HIV suppression assays showed clear differences between VC and NC. HIV suppressive activity, mediated by either ex vivo unstimulated CD8+ T cells or HIVp24-specific T-cell lines, was significantly greater using cells from VC than NC cells. Additionally, we were able to demonstrate a significant correlation between the level of HIV suppressive activity mediated by ex vivo unstimulated CD8+ T cells and plasma viral load (pVL) (Spearman r = -0.7345, p = 0.0003). This study provides evidence that in vitro HIV suppression assays are the most informative in the functional evaluation of CD8+ T-cell responses and can distinguish between VC and NC

Prognostic value of plasma EBV DNA for nasopharyngeal cancer patients during treatment with intensity-modulated radiation therapy and concurrent chemotherapy

Plasma EBV DNA concentrations at the time of diagnosis (pre-EBV) and post treatment (post-EBV) have significant value for predicting the clinical outcome of nasopharyngeal cancer (NPC) patients. However, the prognostic value of the EBV concentration during radiation therapy (mid-EBV) has not been vigorously studied

<i>In vitro</i> HIV suppression assay.

<p><b>(A)</b><i>In vitro</i> HIV suppression assay mediated by <i>ex vivo</i> unstimulated CD8⁺ T cells in VC (N = 10, filled circle), NC (N = 10, open rectangle), and healthy volunteers (HD, N = 9, filled triangle) cocultured with autologous HIV-infected CD4⁺ T cells at E:T ratio of 1:1 at day 7. <b>(B)</b><i>In vitro</i> HIV suppression assay mediated by HIVp24-specific T cell lines from VC (N = 4, filled circle) and NC (N = 7, open rectangle) cocultured with autologous HIV-infected CD4⁺ T cells at E:T ratio of 1:1 at day 3. <b>(C)</b> Percentages of <i>ex vivo</i> HIV-infected CD4⁺ T cells (CD3^posCD8^negP24^pos) in VC (N = 8, filled circle) and NC (N = 13, open rectangle) <b>(D)</b> Production of newly-generated HIV from CD4⁺ T cells from VC (N = 5, filled circle) and NC (N = 5, open rectangle) at day 7. The Y-axis depicts the concentration of HIVp24 Ag (pg/ml) from ELISA assays. *p value <0.05 and ***p value<0.001.</p

Correlation between HIV suppressive activity and pVL.

<p><i>In vitro</i> HIV suppression assay mediated by <i>ex vivo</i> unstimulated CD8⁺ T cells at E:T ratio of 1:1 from HIV-infected volunteers (N = 19) were shown on the X-axis as percentages of HIV suppression. The pVL at the same time-point as the HIV suppression assay are presented on the Y-axis. Each symbol represents a single HIV-infected volunteer. Filled circles and open rectangles represent viraemic controllers and noncontrollers, respectively. Spearman’s rank test was analyzed as the statistic.</p