Long-Term Thermostabilization of Live Poxviral and Adenoviral Vaccine Vectors at Supraphysiological Temperatures in Carbohydrate Glass

Abstract

Live recombinant viral vectors based on adenoviruses and poxviruses are among the most promising platforms for development of new vaccines against diseases such as malaria, tuberculosis, and HIV-AIDS. Vaccines based on live viruses must remain infectious to be effective, so therefore need continuous refrigeration to maintain stability and viability, a requirement that can be costly and difficult, especially in developing countries. The sugars sucrose and trehalose are commonly used as stabilizing agents and cryoprotectants for biological products. Here, we have exploited the ability of these sugars to vitrify on desiccation to develop a thermostabilization technique for live viral vaccine vectors. By slowly drying vaccines suspended in solutions of these disaccharide stabilizers onto a filter-like support membrane at ambient temperature, an ultrathin glass is deposited on the fibers of the inert matrix. Immobilization of two recombinant vaccine vectors-E1/E3-deleted human adenovirus type 5 and modified vaccinia virus Ankara-in this glass on the membranes enabled complete recovery of viral titer and immunogenicity after storage at up to 45 degrees C for 6 months and even longer with minimal losses. Furthermore, the membrane carrying the stabilized vaccine can be incorporated into a holder attached to a syringe for almost simultaneous reconstitution and injection at point of use. The technology may potentially be developed for the deployment of viral vector-based biopharmaceuticals in resource-poor settings.

Langerin negative dendritic cells promote potent CD8 + T-cell priming by skin delivery of live adenovirus vaccine microneedle arrays

“…This modality brought additional challenges: maintaining conformation of the rAdHu5 capsid proteins sufficient to enable virus host receptor binding, internalization, and nuclear targeting coupled with integrity of the adenoviral genome to enable transcriptional competence for Ag expression. Slow drying rAdHu5 vectors in a sucrose formulation to a dry state demonstrated no loss in transgene immunogenicity for at least 1 mo after reconstitution, in agreement with a previous report (25). Crucially, to enable greater practical applicability in the field, we advanced this approach by incorporation of a stabilized rAdHu5 HIV-1 gag vaccine vector within the matrix of a dissolvable MA, thus removing the necessity for vaccine reconstitution and hypodermic needle delivery.…”

Delivery strategies to enhance oral vaccination against enteric infections

“…Strategies to increase the temperature stability of vaccine components are required in parallel with innovative delivery strategies. In this context, the process of vitrification [22] to enhance stability is an attractive strategy, possibly combined with approaches such as gastric resistant microcapsules [23]. As with other oral delivery strategies it will be essential that the priorities of thermostabilisation and gastrointestinal delivery challenges are addressed in an integrated manner.…”

Improving the reach of vaccines to low-resource regions, with a needle-free vaccine delivery device and long-term thermostabilization

“…Advances are being made to improve vaccine thermal stability, but they primarily still rely on the needle and syringe for delivery [2,4] -which hinders safe and effective vaccination, particularly in the developing world. For example, most vaccines delivered by needle and syringe into muscle, where there are relatively few professional antigen presenting cells in comparison with skin and lymph nodes.…”