A Triple Combination HIV Microbicide

The HIV-positive population continues to rise despite a worldwide decline in the rates of infection caused by human immunodeficiency virus (HIV).  The HIV virus continues to spread due to a lack of effective vaccines and pre-exposure prophylaxis methods, even though the availability and effectiveness of antiretroviral therapy has helped reduce acquired immunodeficiency syndrome (AIDS)-related deaths. 

Enhanced Immunogenicity Against HIV-1 Using a DNA-prime Poxvirus Vaccination

Researchers at the National Cancer Institute (NCI) have developed a method of stimulating an immune response in humans at risk for infection by, or already infected with, an Human Immunodeficiency Virus (HIV)-1 retrovirus. This method utilizes deoxyribonucleic acid (DNA) vaccines to stimulate CD8+ T cell immune responses. The DNA vaccine encodes antigens known to be effective against retroviruses, such as HIV-1gag, gp120, nefCTL, and proCTL. The same antigens are also expressed by the pox virus vaccine, which elicits an increased immune response when combined with the DNA vaccine.

Improved HIV Vaccines Through Ras Activation

Researchers at the National Cancer Institute (NCI) have developed a new method of improving the efficacy of vaccines in patients with human immunodeficiency virus (HIV) by activating Ras. This method can be used to develop more efficacious vaccine compositions by activating Ras before, during, or after vaccination. Additionally, the researchers discovered that modulation of the Ras pathways could be a predictive biomarker of protection against HIV.

Renal Selective Unsaturated Englerin Analogues

Englerin A, a natural product, has shown growth-inhibiting activity against renal cancer cell lines. The compound is an agonist of protein kinase C (PCK) theta, which results in cell cytotoxicity, insulin inhibition, and selective activation of viral replication in T cells.  Englerin A derivatives are promising treatment strategies for any diseases associated with PKC theta and/or ion channel proteins.

Fusion Proteins as HIV-1 Entry Inhibitors

Soluble forms of human CD4 (sCD4) inhibit HIV-1 entry into immune cells.  Different forms of sCD4 and their fusion proteins have been extensively studied as promising HIV-1 inhibitors – including in animal models and clinical trials.  However, they have not been successful in human studies due to their transient efficacy.  sCD4 is also known to interact with class II major histocompatibility complex (MHCII) and, at low concentrations, could enhance HIV-1 infectivity. 

Scytovirin Domain 1 Related Polypeptides

Despite therapeutic advances, human immunodeficiency virus (HIV) is still a pervasive disease, with approximately 37 million people infected worldwide. Peptides have become popular therapeutic agents, as these proteins offer structural diversity for many different diseases. Several peptides were commercially developed as HIV therapeutics, demonstrating the high potential for peptides in treating HIV. 

A peptide hydrogel for use in vascular anastomosis

In collaboration with surgery specialists from Johns Hopkins University, researchers at the National Cancer Institute (NCI) developed novel hydrogel compositions and methods of using them in the microsurgical suturing of blood vessels, which is particularly beneficial for surgeons in whole tissue transplant procedures. The lead candidate electropositive hydrogels, called APC1, was demonstrated in anastomosis mice models to be well tolerated, biocompatible, and non-toxic.

Conserved Elements Vaccine for HIV

The development of an effective HIV vaccine has been an ongoing area of research. High variability in HIV-1 virus strains, however,  represents a major challenge.  Ideally, an effective candidate vaccine would provide protection against the majority of clades of HIV.  Two major hurdles to overcome are immunodominance and sequence diversity. Researchers at the National Cancer Institute (NCI) have developed a vaccine that overcomes these major hurdles by utilizing a strategy that identifies conserved regions of the virus and exploits them for use in a targeted therapy.