Evaluasi Potensi Protein Kimera L1L2 HPV Tipe 52 sebagai Kandidat Vaksin Kanker Serviks secara In Vivo

Abstract

Human Papillomavirus (HPV) tipe risiko tinggi merupakan penyebab utama kanker serviks pada wanita, yang mengakibatkan lebih dari 300.000 kematian setiap tahunnya di seluruh dunia. Vaksinasi HPV telah terbukti efektif mencegah infeksi yang disebabkan oleh virus-virus ini, dengan penggunaan luas vaksin protein rekombinan berbasis L1. Namun, vaksin berbasis L1 hanya memberikan perlindungan terhadap tipe HPV tertentu dan memiliki spektrum cakupan yang terbatas. Oleh karena itu, penelitian ini bertujuan untuk mengembangkan vaksin HPV berbasis protein rekombinan kimerik L1L2 dari HPV tipe 52, yang diharapkan dapat meningkatkan netralisasi silang terhadap berbagai tipe HPV. Penelitian ini menggunakan Escherichia coli BL21 (DE3) sebagai sistem ekspresi untuk memproduksi protein rekombinan kimerik L1L2. Lima kelompok mencit betina BALB/c diimunisasi dengan kandidat vaksin tersebut, dan respons imun dievaluasi menggunakan ELISA serta uji netralisasi pseudovirus. Hasil penelitian menunjukkan bahwa kandidat vaksin memicu respons imun terhadap protein HPV, meskipun kinerja antibodi penetral masih perlu ditingkatkan. Uji toksisitas tidak menunjukkan adanya kerusakan signifikan pada organ hati dan ginjal mencit, yang mengindikasikan keamanan kandidat vaksin tersebut. Selanjutnya protein kimera L1L2 diuji pada 4 ekor Macaca fascicularis betina. Dilakukan uji flowcytometri, ELISA dan uji darah lengkap diawal dan akhir penelitian. Berdasarkan temuan ini, protein vaksin kimera L1L2 menunjukkan potensi sebagai alternatif pencegahan kanker serviks. Akan tetapi, optimalisasi lebih lanjut diperlukan untuk meningkatkan efikasinya.

Human Papillomavirus (HPV) of high-risk types are the primary cause of cervical cancer in women, leading to resulting in over 300,000 deaths annually worldwide. HPV vaccination has proven demonstrated effective efficacy in preventing infections caused by these viruses, with L1-based recombinant protein vaccines being widely utilized. However, L1-based vaccines provide protection only against specific HPV types and have a limited coverage spectrum. Therefore consequently, this study aims to develop an HPV vaccine based on a recombinant chimeric L1L2 protein from HPV type 52, which is expected anticipated to enhance cross-neutralization against multiple HPV types. This research used Escherichia coli BL21 (DE3) as the expression system for producing the L1L2 chimeric recombinant protein. Five groups of female BALB/c mice were immunized with the vaccine candidate, and immune responses were evaluated assessed using ELISA and Pseudovirus Neutralization Assays. The results demonstrated outcomes indicated that the vaccine candidate elicited induced an immune response against HPV proteins, albeit with room for improvement although the neutralizing antibody performance still requires improvement. Toxicity tests showed revealed no significant damage to the liver and kidney organs of the mice, suggesting that the vaccine candidate’s is safesafety. Subsequently, the L1L2 chimeric protein was tested on four female Macaca fascicularis. Flow cytometry, ELISA, and complete blood count analyses were performed at the beginning and end of the study. After that Based on these findings, the L1L2 chimeric vaccine proteins shows potential as an alternative for cervical cancer prevention. HoweverNevertheless, further optimization is necessary to enhance its efficacy.