NCI Resources for Cancer Immunoprevention Research.

Cancer prevention and early detection, the first two of the eight primary goals of the National Cancer Plan released in April 2023, are at the forefront of the nation's strategic efforts to reduce cancer incidence and mortality. The Division of Cancer Prevention (DCP) of the NCI is the federal government's principal component devoted to promoting and supporting innovative cancer prevention research. Recent advances in tumor immunology, cancer immunotherapy, and vaccinology strongly suggest that the host immune system can be effectively harnessed to elicit protective immunity against the development of cancer, that is, cancer immunoprevention. Cancer immunoprevention may be most effective if the intervention is given before or early in the carcinogenic process while the immune system remains relatively uncompromised. DCP has increased the emphasis on immunoprevention research in recent years and continues to expand program resources and interagency collaborations designed to facilitate research in the immunoprevention field. These resources support a wide array of basic, translational, and clinical research activities, including discovery, development, and validation of biomarkers for cancer risk assessment and early detection (Early Detection Research Network), elucidation of biological and pathophysiological mechanistic determinants of precancer growth and its control (Translational and Basic Science Research in Early Lesions), spatiotemporal multiomics characterization of precancerous lesions (Human Tumor Atlas Network/Pre-Cancer Atlas), discovery of immunoprevention pathways and immune targets (Cancer Immunoprevention Network), and preclinical and clinical development of novel agents for immunoprevention and interception (Cancer Prevention-Interception Targeted Agent Discovery Program, PREVENT Cancer Preclinical Drug Development Program, and Cancer Prevention Clinical Trials Network).

Comprehensive immunoprofiling and systematic adjuvant comparisons for identifying suitable vaccine: Adjuvant pairings.

Adjuvants are critical components of vaccines that enhance the host immune response to the vaccine antigen, however, only a small number of adjuvants are used in vaccines approved for human use. This is in part due to the slow process of novel adjuvants advancing from preclinical models to human studies, and modest mechanistic insights obtained using standard immunological methods to justify selection of a particular adjuvant for clinical evaluation. Here, we discuss several aspects of current adjuvant research and strategies to better assess the complex pathways triggered by adjuvant candidates that can increase adjuvanticity and vaccine efficacy while minimizing reactogenicity. We propose a more systematic use of broad immunoprofiling, coupled with data integration using computational and mathematical modeling. This comprehensive evaluation of the host immune response will facilitate the selection of the most appropriate adjuvant for a vaccine, ultimately leading to the expeditious evaluation of novel adjuvants for vaccines against emerging infectious diseases, which will prove especially valuable during a pandemic where speed is of the essence when developing vaccines.

Neutralizing antibody patterns and viral escape in HIV-1 non-B subtype chronically infected treatment-naive individuals.

Here we studied the patterns of generation of neutralizing antibodies (NAbs) and virus escape during non-B subtype HIV-1 chronic infection among asymptomatic patients, and established whether a correlation exists between the generation of NAbs and the kinetics of CD4 T-cell decline. Therefore, sequential viruses and plasma obtained at 6 months to one year intervals over a three years period from ten HIV-1 group M subtype A, CRF02_AG, G, and H infected treatment-naïve individuals were tested in neutralization assays. Overall, NAbs were present in all ten individuals, and had the capacity to neutralize autologous virus obtained six months earlier. Eight of the ten subjects showed an increasing capacity to neutralize early viruses and a low capacity to neutralize contemporaneous and later time-point viruses. The neutralizing activities within these individuals resulted in emergence of neutralization resistant viruses, and with the subsequent generation of more NAbs to the emerging resistant viruses. In the remaining two individuals, the capacity to neutralize early, contemporaneous, and later time-point viruses remained conserved. While the kinetics of CD4 T-cell decline varied among all ten individuals, there was no correlation with the capacity to generate NAbs in that, sequential plasmas from individuals with moderately or rapidly declining CD4 T-cells were capable of neutralizing early sequential viruses. We conclude from this study that in non-B subtype chronically infected asymptomatic patients with moderately and rapidly declining CD4 T-cells, potent NAbs are readily generated as the virus evolves to escape the effect of these antibodies.