Background RTS,S/AS01, the leading malaria vaccine has been recommended by the WHO for widespread immunization of children at risk. RTS,S/AS01-induced anti-CSP IgG antibodies are associated with the vaccine efficacy. Here, the long-term kinetics of RTS,S/AS01-induced antibodies was investigated. Methods 150 participants were randomly selected from the 447 children who participated in the RTS,S/AS01 phase IIb clinical trial in 2007 from Kilifi-Kenya. Cumulatively, the retrospective follow-up period was 93 months with annual plasma samples collection. The levels of anti-CSP IgM, total IgG, IgG1, IgG2, IgG3, and IgG4 antibodies were then determined using an enzyme-linked immunosorbent assay. Results RTS,S/AS01 induced high levels of anti-CSP IgG antibodies which exhibited a rapid waning over 6.5 months post-vaccination, followed by a slower decay over the subsequent years. RTS,S/AS01-induced anti-CSP IgG antibodies remained elevated above the control group levels throughout the 7 years follow-up period. The anti-CSP IgG antibodies were mostly IgG1, IgG3, IgG2, and to a lesser extent IgG4. IgG2 predominated in later timepoints. RTS,S/AS01 also induced high levels of anti-CSP IgM antibodies which increased above the control group levels by month 3. The controls exhibited increasing levels of the anti-CSP IgM antibodies which caught up with the RTS,S/AS01 vaccinees levels by month 21. In contrast, there were no measurable anti-CSP IgG antibodies among the controls. Conclusion RTS,S/AS01-induced anti-CSP IgG antibodies kinetics are consistent with long-lived but waning vaccine efficacy. Natural exposure induces anti-CSP IgM antibodies in children, which increases with age, but does not induce substantial levels of anti-CSP IgG antibodies.
Background: Kenya introduced the monovalent Rotarix® rotavirus group A (RVA) vaccine nationally in mid-2014. Long-term surveillance data is important prior to wide-scale vaccine use to assess the impact on disease and to investigate the occurrence of heterotypic strains arising through immune selection. This report presents baseline data on RVA genotype circulation patterns and intra-genotype genetic diversity over a 7-year period in the pre-vaccine era in Kilifi, Kenya, from 2002 to 2004 and from 2010 to 2013. Methods: A total of 745 RVA strains identified in children admitted with acute gastroenteritis to a referral hospital in Coastal Kenya, were sequenced using the di-deoxy sequencing method in the VP4 and VP7 genomic segments (encoding P and G proteins, respectively). Sequencing successfully generated 569 (76%) and 572 (77%) consensus sequences for the VP4 and VP7 genes respectively. G and P genotypes were determined by use of BLAST and the online RotaC v2 RVA classification tool. Results: The most common GP combination was G1P[8] (51%), similar to the Rotarix® strain, followed by G9P[8] (15%) , G8P[4] (14%) and G2P[4] (5%). Unusual GP combinations—G1P[4], G2P[8], G3P[4,6], G8P[8,14], and G12P[4,6,8]—were observed at frequencies of <5%. Phylogenetic analysis showed that the infections were caused by both locally persistent strains as evidenced by divergence of local strains occurring over multiple seasons from the global ones, and newly introduced strains, which were closely related to global strains. The circulating RVA diversity showed temporal fluctuations both season by season and over the longer-term. None of the unusual strains increased in frequency over the observation period. Conclusions: The circulating RVA diversity showed temporal fluctuations with several unusual strains recorded, which rarely caused major outbreaks. These data will be useful in interpreting genotype patterns observed in the region during the vaccine era.
The most important soil-transmitted helminths (STHs) affecting humans are roundworms, whipworms, and hookworms, with a large proportion of the world’s population infected with one or more of these intestinal parasites. On top of that, concurrent infections with several viruses, bacteria, protozoa, and other helminths such as trematodes are common in STH-endemic areas. STHs are potent immunomodulators, but knowledge about the effects of STH infection on the direction and extent of coinfections with other pathogens and vice versa is incomplete. By focusing on Kenya, a country where STH infections in humans are widespread, we provide an exemplary overview of the current prevalence of STH and co-occurring infections (e.g. with Human Immunodeficiency Virus, Plasmodium falciparum, Giardia duodenalis and Schistosoma mansoni). Using human data and complemented by experimental studies, we outline the immunomechanistic interactions of coinfections in both acutely STH transmigrated and chronically infected tissues, also highlighting their systemic nature. Depending on the coinfecting pathogen and immunological readout, STH infection may restrain, support, or even override the immune response to another pathogen. Furthermore, the timing of the particular infection and host susceptibility are decisive for the immunopathological consequences. Some examples demonstrated positive outcomes of STH coinfections, where the systemic effects of these helminths mitigate the damage caused by other pathogens. Nevertheless, the data available to date are rather unbalanced, as only a few studies have considered the effects of coinfection on the worm’s life cycle and associated host immunity. These interactions are complex and depend largely on the context and biology of the coinfection, which can act in either direction, both to the benefit and detriment of the infected host.
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