Dewi Anggraini
1) Arifin Achmad General Hospital, Riau Province, Pekanbaru, Indonesia 2) Eka Hospital Pekanbaru, Pekanbaru, Indonesia 3) Department Of Microbiology, Faculty Of Medicine, Universitas Riau, Pekanbaru, Indonesia

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Impact of DENV Genotypic Variation on Vaccine Efficacy and Cross-Neutralizing Antibody Responses: A Meta-Analysis Utari Gusti Yulimdra; Dewi Anggraini; Fauzia Andrini Djojosugito
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 10 No. 6 (2026): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v10i6.1603

Abstract

Background: The development of a broadly protective dengue virus (DENV) vaccine remains a paramount global health priority. Current tetravalent vaccines target the four DENV serotypes. However, intra-serotypic genetic variations, defined as genotypes, present a neglected immunological barrier. Evidence indicates that genotypic divergence critically impairs cross-neutralizing antibody responses, leaving vaccinated individuals vulnerable to circulating heterologous genotypes and severe antibody-dependent enhancement (ADE). This meta-analysis quantifies the impact of DENV genotypic variation on neutralizing antibody efficacy. Methods: A systematic review and meta-analysis adhering to PRISMA guidelines were conducted. Quantitative virological data were extracted from primary studies, focusing on neutralizing antibody titers against homologous versus heterologous DENV genotypes. A DerSimonian-Laird random-effects model calculated the pooled Standardized Mean Difference (SMD) and 95% Confidence Intervals (CI). Heterogeneity was addressed through subgroup analyses (by serotype and host species). A sensitivity analysis employing the Hartung-Knapp-Sidik-Jonkman (HKSJ) adjustment verified robustness. Risk of bias was evaluated utilizing RoB 2 and SYRCLE tools. Results: Ten controlled studies met the inclusion criteria. The pooled analysis revealed a severe, statistically significant reduction in neutralization capacity against heterologous genotypes compared to homologous strains, yielding an overall SMD of -1.52 (95% CI: -1.95 to -1.09, p < 0.001). High initial heterogeneity (I2 = 84.1%) was partially resolved by stratifying by serotype; the DENV-2 subgroup demonstrated the most profound neutralization deficit (SMD = -1.78, I2 = 42.5%). Sensitivity analyses confirmed the stability of the pooled effect. Conclusion: Vaccine-induced neutralizing responses are significantly attenuated against heterologous DENV genotypes. The prevailing serotype-level vaccine paradigm is insufficient for comprehensive global immunity. Next-generation vaccine designs must incorporate conserved, pan-genotypic epitopes to prevent intra-serotypic immune evasion and subsequent ADE-mediated severe disease.
Bioinformatics Analysis of Potential Targets of Betulinic Acid Against Virulence Factors of Chlamydia trachomatis Erla Nurani; Putri Diana Roza; Darmawi Darmawi; Lalu Muhammad Irham; Wirawan Adikusuma; Dewi Anggraini
Jurnal Ilmiah Kesehatan (JIKA) Vol. 7 No. 3 (2025): Volume 7 Nomor 3 Desember 2025
Publisher : Sarana Ilmu Indonesia (Salnesia)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.36590/jika.v7i3.1465

Abstract

Chlamydia trachomatis is an obligate intracellular pathogen responsible for trachoma and sexually transmitted infections, with rising antibiotic resistance posing a major therapeutic challenge. Natural compounds such as betulinic acid, a pentacyclic triterpenoid with broad-spectrum antimicrobial and anti-inflammatory properties, offer potential as alternative therapeutic agents. This study aimed to analyze the potential targets of betulinic acid against C. trachomatis virulence factors using bioinformatics approaches. Protein–compound interaction prediction was performed using STITCH v5.0, while virulence classification was analyzed through VICMpred and VirulentPred. BepiPred v2.0 was employed to identify B-cell epitopes, and PSORTb v3.0 was used to predict subcellular localization. The results identified five proteins targeted by betulinic acid, including DNA topoisomerase IV subunit B (parE), DNA topoisomerase IV subunit A (parC), DNA gyrase subunits (gyrA and gyrB), and sulfite reductase (cysJ). Among these, three were classified as virulence factors: parE (0,2959), parC (0,1754), and cysJ (0,4018). Subcellular localization analysis showed that parE and parC are cytoplasmic proteins essential for DNA replication, while cysJ is associated with the cytoplasmic membrane and metabolic processes. Betulinic acid showed strong potential as an antimicrobial compound targeting key virulence proteins of C. trachomatis. These findings provide foundational insight for further experimental studies to develop betulinic acid–based therapeutic strategies against chlamydial infections.
Co-Authors Adrianison Adrianison Afladhanti, Putri M. Aisyah Elliyanti Amalia, Aisyah Sabrina Atya Nasmah Bet, Anwar Citra Ayu Anggreli Daenansya, Raehan Dani Rosdiana Darmawi Darmawi Dedi Satriya Putra Dina Fauzia Dino Irawan Effendi, Dasril Eka Zulya Syahputri Ekky Wibisono Erla Nurani Erwin Christianto Erwin Christianto Fadhia Alya Putri Fani, Rifia Tiara Farah Mardhiyah Fauzia Andrini Fauzia Andrini Djojosugito Galuh Tiara Akbar Gusti Yulindra, Utari Hanifah, Zulfa N. hanifah, zulfa nur Hawa Gebriella Hidayat, Nopian INDRA YOVI Insan Fitriyani Jazil Karimi Karina " Karina Karina Kasih, Rani Rindang Lalu Muhammad Irham Marlina Tasril Maya Savira Muhamad Afham Muhammad Ihsan Mukhyarjon Nafisa Khansa Luthfiyah Namira, Syafira Nihla Naufal Mulia Muharram Nazardi Oyong Nazardi Oyong Nori Purnama Nur Afrainin Syah Nurfadila Nurfi Pratiwi, Nurfi Nurul Mawaddah Pratiwi, Adelia Putri Diana Roza Putri, Frilianty Putri, Yolanda Julia Perel Rachmaliza Rachmaliza Ridha Restila Rika Wandari Rita Endriani Riza Yefri Riza Yefri, Riza Rosantia Sarassari Ruza Prima Rustam, Ruza Prima Sabella Gustika Vernanda Safari, Dodi Saukhan, Ghiandra NS Shapira, Vanesya Zahrani Sholihin, Uswathun Hasanah Simanjuntak, Arya M. Simatupang, Elvando Tunggul Mauliate Siska Alya Adha Siti Nurkasanah Sony " Sri Indah Indriani Sri Utari Masyitah Sundari Sundari Suprayoga, Tito Suyanto Suyanto Syah, Nur A. Syahputri, Eka Zulya Syam, Shaogi Talitha Salwa Adriya Triani, Zhana Daisya Tuti Restuastuti Utari Gusti Yulimdra Venty Rahman Wahyu Agung Prasetyo Wardana, Rexi Dwi Wijaya, Dewi Wirawan Adikusuma Yuana Nurulita Zafran Nopala Armindra