Evaluation of the thermal stability and the protective efficacy of spray-dried HPV vaccine, Gardasil® 9

Abstract

High-risk human papillomavirus (HPV) types are responsible for nearly all cases of cervical cancers. Cervarix® and Gardasil® 9 are the current prophylactic vaccines available that protect against the majority of HPVs associated with cancer. Although these vaccines are highly effective, HPV vaccine implementation has been slow, particularly in low-and-middle income countries. Major barriers to the widespread availability of the HPV vaccines is its cost and the requirement for continuous refrigeration (2-8°C). Here, we used spray drying along with stabilizing excipients to formulate a thermostable Gardasil® 9 vaccine. We evaluated the immunogenicity and protective efficacy of the vaccine in mice immediately after spray drying and following storage for three months at 4°C, 25°C, and 40°C. The immunogenicity studies were performed using Gardasil® 9 as a whole antigen, and not individual HPV types, for ELISA. At the dose tested, the spray dried vaccine conferred protection against HPV following storage at temperatures up to 40°C. In addition to the spray-dried vaccine, our studies revealed that the Gardasil® 9 vaccine, as currently marketed, may be stored and transported at elevated temperatures for up to 3 months without losing efficacy, especially against HPV16. This study is critical, as a thermostable vaccine will decrease vaccine cost associated with cold-chain maintenance and could increase vaccine access and coverage, especially in remote regions of the world.

How the use of vaccines outside the cold chain or in controlled temperature chain contributes to improving immunization coverage in low- and middle-income countries (LMICs): A scoping review of the literature

“…There are currently many potentially thermostable vaccines or exploration of the feasibility for using these vaccines CTC in the pipeline including Cholera vaccines [ 33 - 38 ], rotavirus vaccines [ 39 , 40 ], inactivated polio vaccines [ 41 ], influenza vaccines [ 42 ], measles vaccines [ 43 ], Human Papilloma Virus (HPV) vaccines including Gardasil spray [ 44 , 45 ], and vaccines as a microneedle patch or spray [ 42 , 44 , 46 - 48 ]. Once these vaccines are approved for use CTC, the landscape of immunization will change for the better.…”

Progress in spray-drying of protein pharmaceuticals: Literature analysis of trends in formulation and process attributes

“…For this, it is not surprising that the spray-drying of diverse types of vaccines has gathered the deep interest of various research groups. [71,[117][118][119][120][121][122][123][124][125][126][127][128][129][130][131][132][133][134][135] In Figure 3, we present the chronological trends of the studies in the spray-drying of protein pharmaceuticals. We can observe an extensive research of peptide hormones during 2002-2011, and their numbers dwindling slightly in recent years.…”

Virus-like Particle-Based L2 Vaccines against HPVs: Where Are We Today?

“…Additionally, studies are required to assess the thermostability of candidate vaccines. Gardasil-9 has recently been shown to be thermostable at temperatures of up to 40 • C for three months [14,82]. Insertion of peptides on VLPs has been shown to decrease the thermostability of chimeric VLPs [83].…”

“…Sequence alignment of L2 (aa 1-135) from different HPV types. Sequence alignment was done using sequences from both high-risk (HPVs 16,18,26,31,33,34,35,39,45,[51][52][53]56,58,59,66,68,73,and 82) and low-risk HPV types (HPVs 6, 11, 43, and 44). Alignment was done using Jalview software.…”