Dissecting Polyclonal Vaccine-Induced Humoral Immunity against HIV Using Systems Serology

Abstract

While antibody titers and neutralization are considered the gold standard for the selection of successful vaccines, these parameters are often inadequate predictors of protective immunity. As antibodies mediate an array of extra-neutralizing Fc-functions, when neutralization fails to predict protection, investigating Fc-mediated activity may help identify immunological correlates and mechanism(s) of humoral protection. Here, we used an integrative approach termed Systems Serology to analyze relationships among humoral responses elicited in four HIV vaccine-trials. Each vaccine regimen induced a unique humoral “Fc-fingerprint”. Moreover, analysis of case:control data from the first moderately protective HIV vaccine trial, RV144, pointed to mechanistic insights into immune complex composition that may underlie protective immunity to HIV. Thus, multi-dimensional relational comparisons of vaccine humoral fingerprints offer a unique approach for the evaluation and design of novel vaccines against pathogens for which correlates of protection remain elusive.

Latently and uninfected healthcare workers exposed to TB make protective antibodies against Mycobacterium tuberculosis

“…Although there were significant differences between the four groups, the only obvious difference between the protective and nonprotective (26) antibody groups was the abundance of IgG3 at days 1 and 3. Antibodies have many functions, only one of which is recognition of specific antigens by the variable portion of the molecule (20,(22)(23)(24), and a recent report suggested that protective effects of anti-TB antibodies may depend on IgA (24). We, therefore, tested the relative abundance of Ig subclasses from the HCWs (Fig.…”

Reevaluation of immune activation in the era of cART and an aging HIV-infected population

“…The LASSO method has been used to identify key variables from large, complex data sets contributing to particular outcomes such as protective HIV vaccine Ab profiles (44) and spontaneous control of HIV disease (45). Here, we used LASSO to resolve predictors of serological responses to TIV in HIV + and HC individuals.…”

The pentameric complex of human Cytomegalovirus: cell tropism, virus dissemination, immune response and vaccine development

“…However, these parameters are often not sufficient to account for protective immunity [84]. On the other hand, protective immunity has been observed in the absence of neutralizing activity, while a critical role in protection from infection has been attributed for both HIV and HCMV to extra-neutralizing antibody functions, such as antibody-dependent cellular cytotoxicity (ADCC) [85,86], antibody-dependent complement deposition (ADCD) [84] and antibody-dependent NK cell activation [87].…”