Schistosoma mansoni PCR+-infected individuals in the Sudan present elevated systemic levels of chemokines when compared to uninfected and egg(+) cohorts
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
Authors: Arndts, K.; Elfaki, T. E. M.; Jelden, N.; Ritter, M.; Wiszniewsky, A.; Katawa, G.; Goreish, I. A.; El Mekki, M. E. Y. A. Atti; Doenhoff, M. J.; Hoerauf, A.; Layland, L. E.
Abstract
Infections with Schistosoma mansoni remain a major health problem in the Sudan where endemic communities, such as those in Kassala and Khartoum states, continue to face severe social-economic difficulties. Our previous immunoepidemiological findings revealed different immune [cytokine and S. mansoni egg (SEA) antibody] profiles in individuals with active infections (eggs in stool n = 110), individuals positive for S. mansoni via polymerase chain reaction (PCR) using sera (SmPCR+ n = 63) and those uninfected (Sm uninf). As antibody responses to eggs and worms are known to change during infection, we have expanded the profiling further by determining levels of adult worm (SWA) antibodies and nine chemokines in the serum of each individual in the three different cohorts. With the exception of C-C motif chemokine ligand (CCL)2, all measured chemokines were significantly higher in SmPCR+ individuals when compared to the egg(+) group and in addition they also presented elevated levels of SWA-specific immunoglobulin (Ig)G2. Multivariable regression analysis further revealed that infection per se was strongly linked to SWA-specific IgG3 levels and CCL5 was strongly associated with a SmPCR+ diagnostic state. In the absence of PCR diagnostics that recognize juvenile worms or schistosomulae motives, identifying schistosome-specific traits should provide better insights into current prevalence rates in endemic communities and, in doing so, take into consideration PCR+ non-egg(+) individuals in current treatment programmes.
Protein-based, but not viral vector alone, HIV vaccine boosting drives an IgG1-biased polyfunctional humoral immune response
JCI INSIGHT
Authors: Fischinger, Stephanie; Shin, Sally; Boudreau, Carolyn M.; Ackerman, Margaret; Rerks-Ngarm, Supachai; Pitisuttithum, Punnee; Nitayaphan, Sorachai; Kim, Jerome H.; Robb, Merlin L.; Michael, Nelson L.; O'Connell, Robert J.; Vasan, Sandhya; Streeck, Hendrik; Alter, Galit
Abstract
The RV144 HIV-1 vaccine trial results showed moderate reduction in viral infections among vaccinees as well as induction of antibody-dependent cellular cytotoxicity and vaccine-specific IgG and IgG3 responses directed at variable loop regions 1 and 2 of the HIV envelope protein. However, with the recent failure of the HVTN 702 clinical trial, comprehensive profiling of humoral immune responses may provide insight for these disappointing results. One of the changes included in the HVTN 702 study was the addition of a late boost, aimed at augmenting peak immunity and durability. The companion vaccine trial RV305 was designed to permit the evaluation of the immunologic impact of late boosting with either the boosting protein antigen alone, the canarypox viral vector ALVAC alone, or a combination of both. Although previous data showed elevated levels of IgG antibodies in both boosting arms, regardless of ALVAC-HIV vector incorporation, the effect on shaping antibody effector function remains unclear. Thus, here we analyzed the antibody and functional profile induced by RV305 boosting regimens and found that although IgG1 levels increased in both arms that included protein boosting, IgG3 levels were reduced compared with the original RV144 vaccine strategy. Most functional responses increased upon protein boosting, regardless of the viral vector-priming agent incorporation. These data suggest that the addition of a late protein boost alone is sufficient to increase functionally potent vaccine-specific antibodies previously associated with reduced risk of infection with HIV.