Biology subjects

Palaga, T.

Publications and source records attributed to Palaga, T..

3 recordsLinked to original sources

bioRxiv2024

New gamma interferon (IFN- g) algorithm for tuberculosis diagnosis in cynomolgus macaques

Tuberculosis (TB) is the first infectious disease to be screened-out from specified pathogen-free cynomolgus macaques (Macaca fascicularis; Mf) using in human pharmaceutical testing. Being either latent or active stage after exposure to the Mycobacterium tuberculosis complex (MTBC), the monkey gamma-interferon release assay (mIGRA) was previously introduced for early TB detection in Mf. However, a high number of indeterminate cases were unexpectedly encountered. The main reasons were a mitogen positive control and an interpretation algorithm. A cohort of 316 Mf exposed to MTBC was tested of two positive mitogen controls [QFT-PHA and a mixture of ConcanavalinA and Pokeweed (ConA+PWM)], and 100 of 316 animals were selected and 26-month followed-up for the establishment of a new mIGRA algorithm for interpretation. As such, the number of indeterminate cases was drastically reduced (80-100%) when the ConA + PWM mixture was used as a positive mitogen control along with a new mIGRA algorithm for interpretation.

microbiology↗

bioRxiv2022

Immunogenicity and Protective Efficacy of a SARS-CoV-2 mRNA Vaccine Encoding Secreted Non-Stabilized Spike Protein in Mice

Establishment of an mRNA vaccine platform in low- and middle-income countries (LMICs) is important to enhance vaccine accessibility and ensure future pandemic preparedness. Here, we describe the preclinical studies of a SARS-CoV-2 mRNA encoding prefusion-unstabilized ectodomain spike protein encapsulated in lipid nanoparticles (LNP) "ChulaCov19". In BALB/c mice, ChulaCov19 at 0.2, 1, 10, and 30 g given 2 doses, 21 days apart, elicited robust neutralizing antibody (NAb) and T cells responses in a dose-dependent relationship. The geometric mean titer (GMT) of micro-virus neutralizing (micro-VNT) antibody against wild-type virus was 1,280, 11,762, 54,047, and 62,084, respectively. Higher doses induced better cross-neutralizing antibody against Delta and Omicron variants. This elicited specific immunogenicity was significantly higher than those induced by homologous prime-boost with inactivated (CoronaVac) or viral vector (AZD1222) vaccine. In heterologous prime-boost study, mice primed with either CoronaVac or AZD1222 vaccine and boosted with 5 g ChulaCov19 generated NAb 7-fold higher against wild-type virus (WT) and was also significantly higher against Omicron (BA.1 and BA.4/5) than homologous CoronaVac or AZD1222 vaccination. AZD1222-prime/mRNA-boost had mean spike-specific IFN{gamma} positive T cells of 3,725 SFC/106 splenocytes, which was significantly higher than all groups except homologous ChulaCov19. Challenge study in human-ACE-2-expressing transgenic mice showed that ChulaCov19 at 1 g or 10 g protected mice from COVID-19 symptoms, prevented SARS-CoV-2 viremia, significantly reduced tissue viral load in nasal turbinate, brain, and lung tissues 99.9-100%, and without anamnestic of Ab response which indicated its protective efficacy. ChulaCov19 is therefore a promising mRNA vaccine candidate either as a primary or a boost vaccination and has entered clinical development.

immunology↗

bioRxiv2018

Monitoring Anti-Pythium insidiosum IgG Antibodies and (1->3)-β-D-Glucan in Vascular Pythiosis

BackgroundDespite aggressive treatment, vascular pythiosis has a mortality rate of 40%. This is due to the delay in diagnosis and lack of effective monitoring tools. To overcome this drawback, serum beta-D-glucan (BG) and P. insidiosum specific antibody (Pi-Ab) were examined as potential monitoring markers in vascular pythiosis.\n\nMethodsA prospective cohort study of vascular pythiosis patients was carried on during January 2010-July 2016. Clinical information and blood samples were collected and evaluated by the BG and Pi-Ab assays. Linear mixed effect models were used to compare BG and Pi-Ab levels. The in vitro susceptibility test was performed in all P. insidiosum isolates from culture positive cases.\n\nResultsA total of 50 patients were enrolled; 45 survived and 5 died during follow-up. The survivors had a significantly shorter time to medical care (p<0.0001) and a significantly shorter waiting time to the first surgery (p<0.0001). There were no differences in BG levels among the groups at diagnosis (p=0.17); however, BG levels among survivors were significantly lower than the deceased group at 0.5 months (p<0.0001) and became undetectable after 3 months. Survivors were able to maintain ELISA value (EV) of Pi-Ab above 8, whereas EV among deceased patients was less than 4. In vitro susceptibility results revealed no synergistic effects between itraconazole and terbinafine.\n\nConclusionsThis study showed that BG and Pi-Ab were potentially valuable markers to monitor the disease after treatment initiation. An unchanged BG level at 2 weeks after surgery should prompt an evaluation for residual disease.

microbiology↗