A third (booster) dose of the inactivated SARS-CoV-2 vaccine elicits immunogenicity and T follicular helper cell responses in people living with HIV.

Introduction: This study sought to explore the immunogenicity of a booster dose of an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in people living with human immunodeficiency virus (HIV) and identify the factors affecting the magnitude of anti-SARS-CoV-2 antibody levels. Materials and methods: A total of 34 people living with HIV (PLWH) and 34 healthy donors (HD) were administered a booster dose of the same SARS-CoV-2 vaccine. Anti-SARS-CoV-2 antibody and immunoglobulin G (IgG) levels were measured using the SARS-CoV-2 S protein neutralizing antibody Enzyme-Linked Immunosorbent Assay (ELISA) and 2019-nCov IgG Chemiluminescent Immunoassay Microparticles, respectively. Spearman correlation analysis was used to measure the correlation between laboratory markers and neutralizing antibody and IgG levels. Peripheral blood mononuclear cells (PBMCs) were extracted from each subject using density gradient centrifugation and the numbers of memory T and T follicular helper (Tfh) cells were determined using flow cytometry. Results: PLWH had a marked reduction in CD4 and B cell levels that was accompanied by a lower CD4/CD8 T cell ratio. However, those who received a supplementary dose of inactivated SARS-CoV-2 vaccines exhibited antibody positivity rates that were analogous to levels previously observed. The booster vaccine led to a reduction in IgG and neutralizing antibody levels and the amplitude of this decline was substantially higher in the PLWH than HD group. Correlation analyses revealed a strong correlation between neutralizing antibody levels and the count and proportion of CD4 cells. Anti-SARS-CoV-2 IgG antibody levels followed a similar trend. The expression of memory T and Tfh cells was considerably lower in the PLWH than in the HD group. Discussion: PLWH had an attenuated immune response to a third (booster) administration of an inactivated SARS-CoV-2 vaccine, as shown by lower neutralizing antibody and IgG levels. This could be attributed to the reduced responsiveness of CD4 cells, particularly memory T and cTfh subsets. CD4 and cTfh cells may serve as pivotal markers of enduring and protective antibody levels. Vaccination dose recalibration may be critical for HIV-positive individuals, particularly those with a lower proportion of CD4 and Tfh cells.

Inactivated SARS-CoV-2 vaccines elicit immunogenicity and T-cell responses in people living with HIV.

BACKGROUNDS: To date, the effects of SARS-CoV-2 vaccines on people living with HIV (PLWH) were mainly focused on messenger RNA (mRNA) and adenovirus vector-based vaccines, and little is known about the effects of inactivated virus-based vaccine. This study was designed to determine the effects of inactivated SARS-CoV-2 vaccines on PLWH. METHODS: Twenty-four HIV-positive individuals and 24 healthy donors (HD) were respectively recruited from Malipo Country People's Hospital and community in Kunming city. Enumeration of lymphocyte and CD4+CD45RO+ memory T cells were evaluated by flow cytometry. Competitive ELISA was used to measure the level of Anti-SARS-CoV-2 neutralization antibody. Spearman or Pearson correlation analysis was used to analyze the relationship between laboratory indicators and neutralization antibodies in PLWH. T-cell responses (Th1, Th2, Th17, Treg) and intracellular expression of cytokines (IL-2 and TNF-α) in CD4 or CD8 were induced by spike protein in SARS-CoV-2 (SARS-2-S) and further measured by intracellular staining. RESULTS: CD4, B cells, CD4+CD45RO+ memory T cells in peripheral blood of PLWH are dramatically decreased in comparison with HD. Importantly, PLWH display comparable neutralizing antibody positive rate to HD after inoculation with inactivated SARS-CoV-2 vaccine. However, PLWH showed weaker responses to vaccines exhibited by lower levels of neutralizing antibodies. Correlation analysis shows that this is possibly caused by low number of CD4 and B cells. Furthermore, SARS-2-S-induced Th2 and Th17 responses are also decreased in PLWH, while no influences on Treg and other cytokines (IL-2, TNF-α and IFN-γ) observed. CONCLUSIONS: PLWH and HD have comparable neutralizing antibodies positive rates, but PLWH display weaker responses to inactivated SARS-CoV-2 vaccines in magnitude, which suggests that a booster dose or dose adjustment are required for HIV-infected individuals, especially for those with lower counts of CD4 T and B cells.

Efficacy and safety of minimal invasive surgery treatment in hypertensive intracerebral hemorrhage: a systematic review and meta-analysis.

BACKGROUND: Recently, minimal invasive surgery (MIS) has been applied as a common therapeutic approach for treatment of hypertensive intracerebral hemorrhage (HICH). However, the efficacy and safety of MIS is still controversial compared with conservative medical treatment or conventional craniotomy. This meta-analysis aimed to systematically assess the safety and efficacy of MIS compared with conservative method and craniotomy in treating HICH patients. METHODS: PubMed, Embase, Web of Science, and Cochrane Controlled Trials Register were used to identify relevant studies on MIS treatment of HICH up to November 2017. This study evaluated Glasgow Outcome Scale (GOS) score, Activities of Daily Living (ADL) score, pulmonary infection rate, mortality rate, and rebleeding rate for patients who underwent MIS, or conservative method, or craniotomy. Subgroup analyses were performed to compare randomization versus non-randomization and large hematoma versus small or mild hematoma. Begg's test and Egger's test were used to determine the potential presence of publication bias. RESULTS: Sixteen studies consisting of 1912 patients were included in this study to compare the efficacy and safety of MIS to conservative method or craniotomy. MIS contributed to a significant improvement on the prognosis of the patients comparing with conservative group or craniotomy group. Patients undergoing MIS had a lower mortality rate when compared to those receiving conservative method. Also, MIS led to a notable reduction of rebleeding rate and an effective improvement of the patient's quality of life by contrast with craniotomy. No obvious difference was found in terms of the pulmonary infection rate among the comparisons of three treatment methods. Randomization is not the potential source of heterogeneity, but hematoma volume may be a risk factor for post-operative mortality rate. No statistical evidence of publication bias among studies was found under most of comparison models. CONCLUSION: This meta-analysis suggests that minimal invasive surgery is an efficient and safe method for the treatment of hypertensive intracerebral hemorrhage, which is associated with a low mortality rate and rebleeding rate, as well as a significant improvement of the prognosis and the quality life of patients when compared with conservative medical treatment or craniotomy.

Expedient Construction of the Hexacycle of Franchetine.

Franchetine, a unique 7,17-seco type of norditerpenoid alkaloid, possesses a highly congested polycyclic architecture coupled with nine stereogenic centers. Here we present an efficient synthetic approach for the intact hexacyclic framework of franchetine from the known tricyle 16 in 20 steps. The synthesis features a diastereoselective 6-exo-tet radical cyclization for construction of ring A and a unique oxidative Wagner-Meerwein-type rearrangement to realize the functionalized [3.2.1] bridging ring CD.