The novel corona virus termed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread throughout the globe at a formidable speed, causing tens of millions of cases and more than one million deaths in less than a year of its report in December 2019. Since then, companies and research institutions have raced to develop SARS-CoV-2 vaccines, ranging from conventional viral and protein-based vaccines to those that are more cutting edge, including DNA- and mRNA-based vaccines. Each vaccine exhibits a different potency and duration of efficacy, as determined by the antigen design, adjuvant molecules, vaccine delivery platforms, and immunization method. In this review, we will introduce a few of the leading non-viral vaccines that are under clinical stage development and discuss delivery strategies to improve vaccine efficacy, duration of protection, safety, and mass vaccination.

therapy combined with chemotherapy triggers immunogenic cell death and antitumor immune responses, resulting in elimination of local, as well as untreated, distant tumors.

Therapeutic cancer vaccines require robust cellular immunity for the efficient killing of tumor cells, and recent advances in neoantigen discovery may provide safe and promising targets for cancer vaccines. However, elicitation of T cells with strong antitumor efficacy requires intricate multistep processes that have been difficult to attain with traditional vaccination approaches. Here, a multifunctional nanovaccine platform has been developed for direct delivery of neoantigens and adjuvants to lymph nodes (LNs) and highly efficient induction of neoantigen-specific T cell responses. A PEGylated reduced graphene oxide nanosheet (RGO-PEG, 20−30 nm in diameter) is a highly modular and biodegradable platform for facile preparation of neoantigen vaccines within 2 h. RGO-PEG exhibits rapid, efficient (15−20% ID/g), and sustained (up to 72 h) accumulation in LNs, achieving >100-fold improvement in LN-targeted delivery, compared with soluble vaccines. Moreover, RGO-PEG induces intracellular reactive oxygen species in dendritic cells, guiding antigen processing and presentation to T cells. Importantly, a single injection of RGO-PEG vaccine elicits potent neoantigen-specific T cell responses lasting up to 30 days and eradicates established MC-38 colon carcinoma. Further combination with anti-PD-1 therapy achieved great therapeutic improvements against B16F10 melanoma. RGO-PEG may serve a powerful delivery platform for personalized cancer vaccination.

◥Purpose: Gliomas are brain tumors with dismal prognoses. The standard-of-care treatments for gliomas include surgical resection, radiation, and temozolomide administration; however, they have been ineffective in providing significant increases in median survival. Antigen-specific cancer vaccines and immune checkpoint blockade may provide promising immunotherapeutic approaches for gliomas.Experimental Design: We have developed immunotherapy delivery vehicles based on synthetic high-density lipoprotein (sHDL) loaded with CpG, a Toll-like receptor-9 agonist, and tumor-specific neoantigens to target gliomas and elicit immunemediated tumor regression.Results: We demonstrate that vaccination with neoantigen peptide-sHDL/CpG cocktail in combination with anti-PD-L1 immune checkpoint blocker elicits robust neoantigen-specific T-cell responses against GL261 cells and eliminated established orthotopic GL261 glioma in 33% of mice. Mice remained tumor free upon tumor cell rechallenge in the contralateral hemisphere, indicating the development of immunologic memory. Moreover, in a genetically engineered murine model of orthotopic mutant IDH1 (mIDH1) glioma, sHDL vaccination with mIDH1 neoantigen eliminated glioma in 30% of animals and significantly extended the animal survival, demonstrating the versatility of our approach in multiple glioma models.Conclusions: Overall, our strategy provides a general roadmap for combination immunotherapy against gliomas and other cancer types.