Immune age and biological age as determinants of vaccine responsiveness among elderly populations: the Human Immunomics Initiative research program

Abstract

The Human Immunomics Initiative (HII), a joint project between the Harvard T.H. Chan School of Public Health and the Human Vaccines Project (HVP), focuses on studying immunity and the predictability of immuneresponsiveness to vaccines in aging populations. This paper describes the hypotheses and methodological approaches of this new collaborative initiative. Central to our thinking is the idea that predictors of age-related non-communicable diseases are the same as predictors for infectious diseases like COVID-19 and influenza. Fundamental to our approach is to differentiate between chronological, biological and immune age, and to use existing large-scale population cohorts. The latter provide well-typed phenotypic data on individuals’ health status over time, readouts of routine clinical biochemical biomarkers to determine biological age, and bio-banked plasma samples to deep phenotype humoral immune responses as biomarkers of immune age. The first phase of the program involves 1. the exploration of biological age, humoral biomarkers of immune age, and genetics in a large multigenerational cohort, and 2. the subsequent development of models of immunity in relation to health status in a second, prospective cohort of an aging population. In the second phase, vaccine responses and efficacy of licensed COVID-19 vaccines in the presence and absence of influenza-, pneumococcal- and pertussis vaccines routinely offered to elderly, will be studied in older aged participants of prospective population-based cohorts in different geographical locations who will be selected for representing distinct biological and immune ages. The HII research program is aimed at relating vaccine responsiveness to biological and immune age, and identifying aging-related pathways crucial to enhance vaccine effectiveness in aging populations.

Immunosenescence and COVID-19

“…However, it is more and more clear that this lower response is not due to the immune system of the elderly, but to the composition of vaccines. It was shown that modification of antigen concentration and especially of the adjuvant concentration and composition in flu, zoster and anti-pneumococci vaccines increases the response of the elderly immune system (titers of protective antibodies) to that similar to obtained in vaccinated young people ( Fielding and Lambert, 2015 , George and Lawrence, 2015 , Goudsmit et al, 2021 , Lal et al, 2015 ). In case of modern mRNA anti-SARS-CoV-2 vaccines, the mRNA in them is not only the information to be translated to antigenic peptide of the virus, but itself serves as an adjuvant recognized by the TLR7/8 in the cells.…”

Cell cycle arrest: A breakthrough in the supportive care of older cancer patients

“…At the very least, this agent appears to be able to prevent anemia and thrombocytopenia in addition to neutropenia and it is reasonable that it may also prevent damage to other mitotic tissues, including the mucosa and hair follicles. It also appears to reverse the immune changes associated with aging, 72 which may prevent the efficacy of immune checkpoint inhibitors in cancer treatment. Other potential advantages of CCA include the use of a single agent to prevent multiple complications, the prevention of anemia‐related fatigue that is a major cause of disability, the avoidance of the complications of myeloid growth factors, such as pain, stem cell competition, and hematological malignancies, and the ability to administer chemotherapy at full dose intensity, even in frail and oldest patients 77‐78 …”

Hematopoietic Stem Cells and the Immune System in Development and Aging

“…These age-related changes in the landscape of antigen presentation skew the balance between different subpopulations of lymphocytes [ 186 , 241 , 246 , 247 , 248 ]. The consequence of this is a decrease in ability of immunity to recognize “self”, “non-self”, and “altered-self”, as well as a decrease in the amplitude of the immune response [ 249 ]. The decrease in antigen presentation and subsequent decline in antigen processing impairs the ability of the immune system to recognize and destroy senescent cells in the body.…”