ABSTRACT
We studied the development and persistence of neutralising antibodies against SARS-CoV-2 ancestral strain, and Delta and Omicron (BA.1 and BA.2) variants in Vietnamese healthcare workers (HCWs) up to 15 weeks after booster vaccination. We included 47 HCWs with different pre-existing immune statuses (group 1 (G1): n=21, and group 2 (G2): n=26 without and with prior breakthrough Delta variant infection, respectively). The study participants had completed primary immunisation with ChAdOx1-S and booster vaccination with BNT162b2. Neutralising antibodies were measured using a surrogate virus neutralisation assay. Of the 21 study participants in G1, neutralising antibodies against ancestral strain, Delta variant, BA.1 and BA.2 were (almost) abolished at month 8 after the second dose, but all had detectable neutralising antibodies to the study viruses at week two post booster dose. Of the 26 study participants in G2, neutralising antibody levels to BA.1 and BA.2 were significantly higher than those to the corresponding viruses measured at week 2 post breakthrough infection and before the booster dose. At week 15 post booster vaccination, neutralising antibodies to BA.1 and BA.2 dropped significantly, with more profound changes observed in those without breakthrough Delta variant infection. Booster vaccination enhanced neutralising activities against ancestral strain and Delta variant, as compared to those induced by primary vaccination. These responses were maintained at high levels for at least 15 weeks. Our findings emphasise the importance of the first booster dose in producing cross-neutralising antibodies against Omicron variant. A second booster dose might be needed to maintain long-term protection against Omicron variant.
ABSTRACT
The identification of small molecules with selective bioactivity, whether intended as potential therapeutics or as tools for experimental research, is central to progress in medicine and in the life sciences. To facilitate such study, we have developed a ligand-based program well-suited for effective screening of large compound collections. This package, MED-SuMoLig, combines a SMARTS-driven substructure search aiming at 3D pharmacophore profiling and computation of the local atomic density of the compared molecules. The screening utility was then investigated using 52 diverse active molecules (against CDK2, Factor Xa, HIV-1 protease, neuraminidase, ribonuclease A, and thymidine kinase) merged to a library of about 40,000 putative inactive (druglike) compounds. In all cases, the program recovered more than half of the actives in the top 3% of the screened library. We also compared the performance of MED-SuMoLig with that of ChemMine or of ROCS and found that MED-SuMoLig outperformed both methods for CDK2 and Factor Xa in terms of enrichment rates or performed equally well for the other targets.
ABSTRACT
Cryptococcus neoformans affections during HIV-infection are frequent and serious. The aim of this study was to analyse the epidemiological, clinical, biological and therapeutic characteristics of cryptococcal meningitis in HIV-positive patients, admitted into the Center for Tropical Diseases Ho Chi Minh City (Vietnam), during a 5-month period (May-September 2001). Twenty-one patients (20 men and one woman) were included (identification of C. neoformans from the cerebrospinal fluid). The mean age was 28 years. The majority of patients had been living in Ho Chi Minh City (48%). The use of drugs and unprotected sexual relations were the principal risk factors of HIV-infection. The paucity and the confusion of clinical signs and symptoms, along with a high frequency of meningitis have been analysed. Clinical presentation features included: headache (95%), emaciation (90%), oro-pharyngeal candidiasis (90%), stiff neck (80%), nausea/vomiting (70%), fever (67%), coughing (38%), diarrhoea (33%), skin lesions (5%), convulsion (5%), photophobia (5%), and hemiparesis (5%). The severity of the prognosis was mainly linked to the delay before hospitalization, to the possible association with other opportunistic infections, and to the availability of appropriate treatment.
