Enhancement of Immune Responses by Guanosine-Based Particles in DNA Plasmid Formulations against Infectious Diseases
JOURNAL OF IMMUNOLOGY RESEARCH
Authors: Santos, Saritza; Ramirez, Maite; Miranda, Eric; Reyes, Nelson; Martinez, Osmarie; Acosta-Santiago, Maxier; Rivera, Jose M.; Otero, Miguel
Abstract
Immunogenicity of DNA vaccines can be efficiently improved by adding adjuvants into their formulations. In this regard, the application of nano- and microparticles as vaccines adjuvants, or delivery systems, provides a powerful tool in designing modern vaccines. In the present study, we examined the role of Supramolecular Hacky Sacks (SHS) particles, made via the hierarchical self-assembly of a guanosine derivative, as a novel immunomodulator for DNA plasmid preparations. These plasmids code for the proteins HIV-1 Gag (pGag), the wild-type vaccinia virus Western Reserve A27 (pA27L), or a codon-optimized version of the latter (pOD1A27Lopt), which is also linked to the sequence of the outer domain-1 (OD1) from HIV-1 gp120 protein. We evaluated the enhancement of the immune responses generated by our DNA plasmid formulations in a murine model through ELISpot and ELISA assays. The SHS particles increased the frequencies of IFN--producing cells in mice independently immunized with pGag and pA27L plasmids. Moreover, the addition of SHS to pGag and pA27L DNA plasmid formulations enhanced the production of IFN- (Th1-type) over IL-4 (Th2-type) cellular immune responses. Furthermore, pGag and pA27L plasmids formulated with SHS, triggered the production of antigen-specific IgG in mice, especially the IgG2a isotype. However, no improvement of either of those adaptive immune responses was observed in mice receiving pOD1A27Lopt+SHS. Here, we demonstrated that SHS particles have the ability to improve both arms of adaptive immunity of plasmid coding wild-type antigens without additional strategies to boost their immunogenicity. To the best of our knowledge, this is the first report of SHS guanosine-based particles as DNA plasmid adjuvants.
Inactivation of HIV-1 Infection through Integrative Blocking with Amino Phenylboronic Acid Attributed Carbon Dots
ACS BIOMATERIALS SCIENCE & ENGINEERING
Authors: Aung, Yu Yu; Kristanti, Alfinda Novi; Khairunisa, Siti Qamariyah; Nasronudin, Nasronudin; Fahmi, Mochamad Zakki
Abstract
Current antiretroviral HIV therapies continue to have problems related to procedural complications, toxicity, and uncontrolled side effects. In this study, amino phenylboronic acid-modified carbon dots (APBA-CDs) were introduced as a new nanoparticle-based on gp120 targeting that inhibits HIV-1 entry processes. Prolonged by simple pyrolysis for preparing carbon dots, this report further explores attributing amino phenylboronic acid on carbon dots, which prove the formation of graphene-like structures on carbon dots and boronic acid sites, thereby enabling the enhancement of positive optical properties through photoluminescent detection. Aside from performing well in terms of biocompatibility and low cytotoxicity (the CC50 reach up to 11.2 mg/mL), APBA-CDs exhibited superior capabilities in terms of prohibiting HIV-1 entry onto targeted MOLT-4 cells recognized by the delimitations of syncitia formation and higher ATP signal rather than bare carbon dots. The modified carbon dots also promote dual-action on HIV-1 treatment by both intracellularly and extracellularly viral blocking by combining with the Duviral drug, along with compressing p24 antigen signals that are better than APBA-CDs and Duviral itself.