Preclinical efficacy, safety, and immunogenicity of PHH-1V, a second-generation COVID-19 vaccine, in non-human primates

SARS-CoV-2 emerged in December 2019 and quickly spread worldwide, continuously striking with an unpredictable evolution. Despite the success in vaccine production and mass vaccination programmes, the situation is not still completely controlled, and therefore accessible second-generation vaccines are required to mitigate the pandemic. We previously developed an adjuvanted vaccine candidate coded PHH-1V, based on a heterodimer fusion protein comprising the RBD domain of two SARS-CoV-2 variants. Here, we report data on the efficacy, safety, and immunogenicity of PHH-1V in cynomolgus macaques. PHH-1V prime-boost vaccination induces high levels of RBD-specific IgG and IgA binding and neutralising antibodies against several SARS-CoV-2 variants of concern, as well as a balanced Th1/Th2 cellular immune response. Remarkably, PHH-1V vaccination prevents SARS-CoV-2 replication in the lower respiratory tract and significantly reduces viral load in the upper respiratory tract after an experimental infection. These results highlight the potential use of the PHH-1V vaccine in humans, currently undergoing Phase III clinical trials.

Preclinical efficacy, safety, and immunogenicity of PHH-1V, a second-generation COVID-19 vaccine candidate based on a novel recombinant RBD fusion heterodimer of SARS-CoV-2.

The current COVID-19 vaccines have been associated with a decline in infection rates, prevention of severe disease and decrease in mortality rates. However, new variants of concern (VoCs) are continuously evolving, making the development of new accessible COVID-19 vaccines essential in order to mitigate the pandemic. Here we present data on preclinical studies in mice of a receptor-binding domain (RBD)-based recombinant protein vaccine candidate (PHH-1V) consisting of an RBD fusion heterodimer containing the B.1.351 and B.1.1.7 SARS-CoV-2 VoCs and formulated with the SQBA adjuvant, an oil-in-water emulsion produced by HIPRA. BALB/c and K18-hACE2 mice were immunized with different recombinant RBD fusion heterodimer doses, following a two-dose prime-and-boost schedule. Vaccination induced a CD4+ and CD8+ T cell response and RBD-binding antibodies with neutralising activity against various VoCs with a good tolerability profile. Significantly, a 10-{micro}g or 20-{micro}g RBD fusion heterodimer/dose vaccination conferred 100% efficacy, preventing mortality in SARS-CoV-2 infected K18-hACE2 mice. These findings demonstrate the feasibility of this recombinant vaccine strategy.

Thermo-responsive hydrogels for cancer local therapy: Challenges and state-of-art.

Despite the enormous efforts done by the scientific community in the last decades, advanced cancer is still considered an incurable disease. New formulations are continuously under investigation to improve drugs therapeutic index, i.e., increase chemotherapeutic efficacy and reduce adverse effects. In this context, hydrogels-based systems for drug local sustained/controlled release have been proposed to reduce off-target effects caused by the repeated administration of systemic/oral anticancer drugs and improve their therapeutic effectiveness. Moreover, it increases the patient welfare by reducing the number of administrations needed. Among the several types of existing hydrogels, the thermo-responsive ones, which are able to change their physical state from liquid at 25 °C to a gel at the body temperature, i.e., 37 °C, gained special attention as in situ sustained drug release depot-systems in cancer treatment. To date, several thermo-responsive hydrogels have been used for drugs and/or genetic material delivery, yielding promising results both at preclinical and clinical evaluation stages. This culminates in the market authorization of Jelmyto® for the treatment of urothelial cancer. Here are summarized and discussed the last 10 years advances regarding the application of thermo-responsive hydrogels in local cancer treatment.

Antibiotics in endophthalmitis: microbiological and pharmacokinetic considerations.

Ocular infections must be treated with active antibiotics which could be administered by different routes: topical, systemic or intravitreal. In the case of endophthalmitis, the most important factor to avoid permanent damage of retina is an early antibiotic onset. Topical application of these drugs would be ineffective in the treatment of endophthalmitis, because of their poor penetration into the ocular globe. Systemic and intravitreal route of administration are the preferred in this setting, although for hydrophilic antibiotics, such as aminoglycosides, beta-lactams and glycopeptides, diffusion from plasma to vitreous cavity is not high enough to assure clinical efficacy. Intravitreal injection should be the favourite route of administration in this case. Ocular penetration of linezolid and fluorquinolones after systemic administration is excellent; hence intravitreal injections for these agents are not needed to achieve therapeutic concentrations at the vitreous cavity.