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Displaying publications 161 - 167 of 167 in total

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Fulltext Immunogenicity and Safety of a Tetravalent Dengue Vaccine Administered Concomitantly or Sequentially With Quadrivalent Human Papillomavirus Vaccine in Boys and Girls 9-13 Years of Age in Malaysia: A Phase IIIb, Randomized, Open-label Study

Hassan J, Toh TH, Sivapunniam SK, Hasim R, Ghazali NF, Sulaiman S, et al.

Pediatr Infect Dis J, 2021 08 01;40(8):774-781.
PMID: 34250977 DOI: 10.1097/INF.0000000000003164

BACKGROUND: Incorporating dengue vaccination within existing vaccination programs could help improve dengue vaccine coverage. We assessed the immunogenicity and safety of a quadrivalent human papillomavirus (HPV) vaccine administered concomitantly or sequentially with a tetravalent dengue vaccine (CYD-TDV) in healthy children 9-13 years of age in Malaysia.
METHODS: In this phase IIIb, open-label, multicenter study (NCT02993757), participants were randomized 1:1 to receive 3 CYD-TDV doses 6 months apart and 2 doses of quadrivalent HPV vaccine concomitantly with, or 1 month before (sequentially), the first 2 CYD-TDV doses. Only baseline dengue-seropositive participants received the 3 doses. Antibody levels were measured at baseline and 28 days after each injection using an enzyme-linked immunosorbent assay for HPV-6, -9, -16 and -18, and the 50% plaque reduction neutralization test for the 4 dengue serotypes; immunogenicity results are presented for baseline dengue-seropositive participants. Safety was assessed throughout the study for all participants.
RESULTS: At baseline, 197 of 528 (37.3%) randomized participants were dengue-seropositive [n = 109 (concomitant group) and n = 88 (sequential group)]. After the last HPV vaccine dose, antibody titers for HPV among baseline dengue-seropositive participants were similar between treatment groups, with between-group titer ratios close to 1 for HPV-6 and 0.8 for HPV-11, -16, and -18. After CYD-TDV dose 3, dengue antibody titers were similar between treatment groups for all serotypes [between-group ratios ranged from 0.783 (serotype 2) to 1.07 (serotype 4)]. No safety concerns were identified.
CONCLUSIONS: The immunogenicity and safety profiles of CYD-TDV and quadrivalent HPV vaccines were unaffected when administered concomitantly or sequentially in dengue-seropositive children.
Fulltext Density Functional Theory Study of 12mer Single-Strand Guanine Oligomer and Associated Muon Hyperfine Interaction

Zaharim WN, Ahmad SNA, Sulaiman S, Rozak H, Hasan Baseri DF, Mohamad Rosli NA, et al.

ACS Omega, 2021 Nov 09;6(44):29641-29650.
PMID: 34778635 DOI: 10.1021/acsomega.1c03956

Density functional theory method at the B3LYP/6-31G level was used to determine the structure of 12mer single-strand guanine oligomers. The length and width of the optimized structure are 38.7 and 18.2 Å, respectively, and the observed high-resolution transmission electron microscopy image of the 12mer single-strand guanine sample shows similar oligomer dimensions with the calculated ones. Both HOMO and LUMO are significantly delocalized, and the calculated HOMO-LUMO gap is 3.31 eV. A total of 96 muonium trapping sites at C2, C4, C5, C6, C8, N3, N7, and O6 were investigated. All 12 C8 sites have lower energy than the other 84 sites and are clustered in the energy-muon hyperfine coupling constant scatter plot. The calculated muon hyperfine coupling constant at C8 sites range from 384.6 to 481.1 MHz, and the corresponding estimated ALC-μSR resonance for |ΔM| = 1 range from 1.419 to 1.775 T.
Chlamydia trachomatis plasmid-encoding Pgp3 protein induces secretion of distinct inflammatory signatures from HeLa cervical epithelial cells

Cheong HC, Cheok YY, Chan YT, Tang TF, Sulaiman S, Looi CY, et al.

BMC Microbiol, 2023 Mar 04;23(1):58.
PMID: 36870960 DOI: 10.1186/s12866-023-02802-3

BACKGROUND: Genital Chlamydia trachomatis infection is the most common bacterial sexual transmitted disease that causes severe complications including pelvic inflammatory disease, ectopic pregnancy, and infertility in females. The Pgp3 protein encoded by C. trachomatis plasmid has been speculated to be an important player in chlamydial pathogenesis. However, the precise function of this protein is unknown and thus remains to be thoroughly investigated.
METHODS: In this study, we synthesized Pgp3 protein for in vitro stimulation in the Hela cervical carcinoma cells.
RESULTS AND CONCLUSION: We showed that Pgp3 induced prominent expression of host inflammatory cytokine genes including interleukin-6 (IL-6), IL-8, tumor necrosis factor alpha-induced protein 3 (TNFAIP3), and chemokine C-X-C motif ligand 1 (CXCL1), implying a possible role of Pgp3 in modulating the inflammatory reaction in the host.
Influx of podoplanin-expressing inflammatory macrophages into the genital tract following Chlamydia infection

Chan YT, Cheok YY, Cheong HC, Tan GMY, Seow SR, Tang TF, et al.

Immunol Cell Biol, 2023 Apr;101(4):305-320.
PMID: 36658328 DOI: 10.1111/imcb.12621

Genital Chlamydia trachomatis infection remains a major health issue as it causes severe complications including pelvic inflammatory disease, ectopic pregnancy and infertility in females as a result of infection-associated chronic inflammation. Podoplanin, a transmembrane receptor, has been previously reported on inflammatory macrophages. Thus, strategies that specifically target podoplanin might be able to reduce local inflammation. This study investigated the expression level and function of podoplanin in a C. trachomatis infection model. C57BL/6 mice infected with the mouse pathogen Chlamydia muridarum were examined intermittently from days 1 to 60 using flow cytometry analysis. Percentages of conventional macrophages (CD11b+ CD11c- F4/80+ ) versus inflammatory macrophages (CD11b+ CD11c+ F4/80+ ), and the expression of podoplanin in these cells were investigated. Subsequently, a podoplanin-knockout RAW264.7 cell was used to evaluate the function of podoplanin in C. trachomatis infection. Our findings demonstrated an increased CD11b+ cell volume in the spleen at day 9 after the infection, with augmented podoplanin expression, especially among the inflammatory macrophages. A large number of podoplanin-expressing macrophages were detected in the genital tract of C. muridarum-infected mice. Furthermore, analysis of the C. trachomatis-infected patients demonstrated a higher percentage of podoplanin-expressing monocytes than that in the noninfected controls. Using an in vitro infection in a transwell migration assay, we identified that macrophages deficient in podoplanin displayed defective migratory function toward C. trachomatis-infected HeLa 229 cells. Lastly, using immunoprecipitation-mass spectrometry method, we identified two potential podoplanin interacting proteins, namely, Cofilin 1 and Talin 1 actin-binding proteins. The present study reports a role of podoplanin in directing macrophage migration to the chlamydial infection site. Our results suggest a potential for reducing inflammation in individuals with chronic chlamydial infections by targeting podoplanin.
CPAF, HSP60 and MOMP antigens elicit pro-inflammatory cytokines production in the peripheral blood mononuclear cells from genital Chlamydia trachomatis-infected patients

Cheong HC, Lee CYQ, Cheok YY, Shankar EM, Sabet NS, Tan GMY, et al.

Immunobiology, 2019 01;224(1):34-41.
PMID: 30477893 DOI: 10.1016/j.imbio.2018.10.010

BACKGROUND: Persistent inflammation caused by Chlamydia trachomatis in the female genital compartment represents one of the major causes of pelvic inflammatory disease (PID), ectopic pregnancy and infertility in females. Here, we examined the pro-inflammatory cytokine response following stimulation with three different types of C. trachomatis antigens, viz. chlamydial protease-like factor (CPAF), heat shock protein 60 (HSP60) and major outer membrane protein (MOMP).
METHODS: A total of 19 patients with genital C. trachomatis infection and 10 age-matched healthy controls were recruited for the study. Peripheral blood mononuclear cells (PBMCs) isolated from genital C. trachomatis-infected females were cultured in the presence of CPAF, HSP60 and MOMP antigens, and cytokines were measured by ELISA assay.
RESULTS: We reported that pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) were robustly secreted following antigenic exposure. Notably, CPAP and MOMP were more potent in triggering IL-1β, as compared to HSP60. Elevated levels of the proinflammatory cytokines were also noted in the samples infected with plasmid-bearing C. trachomatis as compared to those infected with plasmid-free strains.
CONCLUSIONS: Our study highlights distinct ability of chlamydial antigens in triggering pro-inflammatory response in the host immune cells.
Fulltext Diversity of endocervical microbiota associated with genital Chlamydia trachomatis infection and infertility among women visiting obstetrics and gynecology clinics in Malaysia

Cheong HC, Yap PSX, Chong CW, Cheok YY, Lee CYQ, Tan GMY, et al.

PLoS One, 2019;14(11):e0224658.
PMID: 31738795 DOI: 10.1371/journal.pone.0224658

The cervical microbiota constitutes an important protective barrier against the invasion of pathogenic microorganisms. A disruption of microbiota within the cervical milieu has been suggested to be a driving factor of sexually transmitted infections. These include Chlamydia trachomatis which frequently causes serious reproductive sequelae such as infertility in women. In this study, we profiled the cervical microbial composition of a population of 70 reproductive-age Malaysian women; among which 40 (57.1%) were diagnosed with genital C. trachomatis infection, and 30 (42.8%) without C. trachomatis infection. Our findings showed a distinct compositional difference between the cervical microbiota of C. trachomatis-infected subjects and subjects without C. trachomatis infection. Specifically, significant elevations of mostly strict and facultative anaerobes such as Streptococcus, Megasphaera, Prevotella, and Veillonella in the cervical microbiota of C. trachomatis-positive women were detected. The results from the current study highlights an interaction of C. trachomatis with the environmental microbiome in the endocervical region.
Fulltext The Glaciozyma antarctica genome reveals an array of systems that provide sustained responses towards temperature variations in a persistently cold habitat

Firdaus-Raih M, Hashim NHF, Bharudin I, Abu Bakar MF, Huang KK, Alias H, et al.

PLoS One, 2018;13(1):e0189947.
PMID: 29385175 DOI: 10.1371/journal.pone.0189947

Extremely low temperatures present various challenges to life that include ice formation and effects on metabolic capacity. Psyhcrophilic microorganisms typically have an array of mechanisms to enable survival in cold temperatures. In this study, we sequenced and analysed the genome of a psychrophilic yeast isolated in the Antarctic region, Glaciozyma antarctica. The genome annotation identified 7857 protein coding sequences. From the genome sequence analysis we were able to identify genes that encoded for proteins known to be associated with cold survival, in addition to annotating genes that are unique to G. antarctica. For genes that are known to be involved in cold adaptation such as anti-freeze proteins (AFPs), our gene expression analysis revealed that they were differentially transcribed over time and in response to different temperatures. This indicated the presence of an array of adaptation systems that can respond to a changing but persistent cold environment. We were also able to validate the activity of all the AFPs annotated where the recombinant AFPs demonstrated anti-freeze capacity. This work is an important foundation for further collective exploration into psychrophilic microbiology where among other potential, the genes unique to this species may represent a pool of novel mechanisms for cold survival.