Differential shaping of T cell responses elicited by heterologous ChAd68/self-amplifying mRNA SIV vaccine in macaques in combination with αCTLA4, αPD-1, or FLT3R agonist.

While therapeutic vaccines are a promising strategy for inducing human immunodeficiency virus (HIV) control, HIV vaccines tested to date have offered limited benefit to people living with HIV. The barriers to success may include the use of vaccine platforms and/or immunogens that drive weak or suboptimal immune responses, immune escape and/or immune dysfunction associated with chronic infection despite effective antiretroviral therapy. Combining vaccines with immune modulators in a safe manner may address some of the challenges and thus increase the efficacy of therapeutic HIV vaccines.

A shared neoantigen vaccine combined with immune checkpoint blockade for advanced metastatic solid tumors: phase 1 trial interim results.

Therapeutic vaccines that elicit cytotoxic T cell responses targeting tumor-specific neoantigens hold promise for providing long-term clinical benefit to patients with cancer. Here we evaluated safety and tolerability of a therapeutic vaccine encoding 20 shared neoantigens derived from selected common oncogenic driver mutations as primary endpoints in an ongoing phase 1/2 study in patients with advanced/metastatic solid tumors. Secondary endpoints included immunogenicity, overall response rate, progression-free survival and overall survival.

Low-dose self-amplifying mRNA COVID-19 vaccine drives strong protective immunity in non-human primates against SARS-CoV-2 infection.

The coronavirus disease 2019 (COVID-19) pandemic continues to spread globally, highlighting the urgent need for safe and effective vaccines that could be rapidly mobilized to immunize large populations. We report the preclinical development of a self-amplifying mRNA (SAM) vaccine encoding a prefusion stabilized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein and demonstrate strong cellular and humoral immune responses at low doses in mice and rhesus macaques. The homologous prime-boost vaccination regimen of SAM at 3, 10 and 30 μg induced potent neutralizing antibody (nAb) titers in rhesus macaques following two SAM vaccinations at all dose levels, with the 10 μg dose generating geometric mean titers (GMT) 48-fold greater than the GMT of a panel of SARS-CoV-2 convalescent human sera.