Methylparaben as a preservative in the development of a multi-dose HPV-2 vaccine

Abstract

ABSTRACT The human papillomavirus (HPV) vaccine is the simplest, most economical, convenient, and effective method of preventing cervical cancer. However, the current HPV vaccine is supplied as a single-dose vial with a relatively high cost per dose, which hinders its supply to low- and middle-income countries (LMICs), where the demand for HPV vaccine is highest. Therefore, it is necessary to develop a multi-dose HPV vaccine to promote large-scale affordable vaccination in LMICs. Moreover, the addition of preservatives is required to reduce the risk of microbial contamination in multi-dose vaccines within a single vial. In this study, we investigated the effects of six preservatives on HPV 16L1 and 18L1 virus-like particles in solution, as well as the aluminum adsorption status, under normal and high-temperature conditions. Multiple methods were employed, including dynamic light scattering, differential scanning calorimetry, an in vitro relative potency assay, and an in vivo potency assay in mice. Based on the above results, four types of selected preservatives were further studied, and an antimicrobial effectiveness test was performed on the HPV-2 vaccine, which was employed as a model HPV vaccine. Finally, three preservatives were selected based on their performance to evaluate the long-term stability of the HPV-2 vaccine. The results indicated that 0.12% methylparaben is the most suitable preservative for the multi-dose HPV-2 vaccine, guaranteeing the shelf life for at least three years and meeting “B” standards for antimicrobial effectiveness. The formula developed in this study can contribute toward combating cervical cancer in LMICs.