Amorphous silica nanoparticles (nSP50) exacerbate hepatic damage through the activation of acquired cell-mediated immunity

Due to their innovative functions, the use of nanoparticles in various industries has been expanding. However, a key concern is whether nanoparticles induce unexpected biological effects. Although many studies have focused on innate immunity, information on whether nanoparticles induce biological responses through effects on acquired immunity is sparse. Here, to assess the effects of amorphous silica nanoparticles on acquired immunity, we analyzed changes in acute toxicities after pretreatment with amorphous silica nanoparticles (50 nm in diameter; nSP50). Pretreatment with nSP50 biochemically and pathologically exacerbated nSP50-induced hepatic damage in immunocompetent mice. However, pretreatment with nSP50 did not exacerbate hepatic damage in immunodeficient mice. Consistent with this, the depletion of CD8+ cells with an anti-CD8 antibody in animals pretreated with nSP50 resulted in lower plasma levels of hepatic injury markers such as ALT and AST after an intravenous administration than treatment with an isotype-matched control antibody. Finally, stimulation of splenocytes promoted the release of IFN-γ in nSP50-pretreated mice regardless of the stimulator used. Moreover, the blockade of IFN-γ decreased plasma levels of ALT and AST levels in nSP50-pretreated mice. Collectively, these data show that nSP50-induced acquired immunity leads to exacerbation of hepatic damage through the activation of cytotoxic T lymphocytes.

Unexposed populations and potential COVID-19 hospitalisations and deaths in European countries as per data up to 21 November 2021

We estimate the potential remaining COVID-19 hospitalisation and death burdens in 19 European countries by estimating the proportion of each country’s population that has acquired immunity to severe disease through infection or vaccination. Our results suggest many European countries could still face high burdens of hospitalisations and deaths, particularly those with lower vaccination coverage, less historical transmission and/or older populations. Continued non-pharmaceutical interventions and efforts to achieve high vaccination coverage are required in these countries to limit severe COVID-19 outcomes.

COVID-19 vaccine coverage and the necessity of its urgent development towards Omicron the new SARS CoV-2 B.1.1. 529 variant

A SARS-CoV-2 variant belonging to Pango lineage B.1.1.529 with a significant number of S-gene mutations compared to the original virus was found in early November 2021. On 26th November 2021, the World Health Organization (WHO) designated the mutation as a variant of concern and assigned it the name Omicron. The difference is identified by 30 changes in the spike protein, three minor deletions, and one minor insertion, 15 of which are in the receptor-binding area. The Omicron variant is the most diverging variety discovered in substantial numbers so far during the pandemic, raising significant concerns that it may be associated with significant reductions in vaccination efficacy and an increased risk of reinfections. Omicron pseudo- or live virus isolates are urgently needed to understand better the virus's escape potential against both vaccination, and infection-acquired immunity is urgently required.

Mutations and Variants of SARS-CoV-2, the Coronavirus Causing COVID-19

In 2020, the SARS-CoV-2 coronavirus caused a pandemic with severe consequences for many countries. The life cycle of the virus is briefly described. It is noted that the multiplication of viral genetic material is accompanied by the emergence of mutations, which leads to the emergence of new viral variants. Viral variants may differ in their effectiveness in infecting, spreading, in the severity of the disease they cause, and in their ability to escape acquired immunity. The most important SARS-CoV-2 variants that have emerged so far are discussed. The need for global monitoring of the emergence of new variants and rapid and mass vaccination to tackle the pandemic is emphasized.

Diversity of Human-Associated Bifidobacterial Prophage Sequences

Members of Bifidobacterium play an important role in the development of the immature gut and are associated with positive long-term health outcomes for their human host. It has previously been shown that intestinal bacteriophages are detected within hours of birth, and that induced prophages constitute a significant source of such gut phages. The gut phageome can be vertically transmitted from mother to newborn and is believed to exert considerable selective pressure on target prokaryotic hosts affecting abundance levels, microbiota composition, and host characteristics. The objective of the current study was to investigate prophage-like elements and predicted CRISPR-Cas viral immune systems present in publicly available, human-associated Bifidobacterium genomes. Analysis of 585 fully sequenced bifidobacterial genomes identified 480 prophage-like elements with an occurrence of 0.82 prophages per genome. Interestingly, we also detected the presence of very similar bifidobacterial prophages and corresponding CRISPR spacers across different strains and species, thus providing an initial exploration of the human-associated bifidobacterial phageome. Our analyses show that closely related and likely functional prophages are commonly present across four different species of human-associated Bifidobacterium. Further comparative analysis of the CRISPR-Cas spacer arrays against the predicted prophages provided evidence of historical interactions between prophages and different strains at an intra- and inter-species level. Clear evidence of CRISPR-Cas acquired immunity against infection by bifidobacterial prophages across several bifidobacterial strains and species was obtained. Notably, a spacer representing a putative major capsid head protein was found on different genomes representing multiple strains across B. adolescentis, B. breve, and B. bifidum, suggesting that this gene is a preferred target to provide bifidobacterial phage immunity.

Acquired clinical immunity to malaria in non-human primates co-infected with Schistosoma and Plasmodium parasites

Background. Naturally acquired immunity to malaria develops over several years and can be compromised by concomitant infections. This study explored the influence of chronic schistosomiasis on clinical outcome and immunity to repeated malaria infection. Methods. Two groups of baboons (n=8 each), were infected with Schistosoma mansoni cercariae to establish chronic infections. One of the two groups was treated with Praziquantel to eliminate schistosome infection. The two groups plus a new malaria control group (n=8), were inoculated three times with Plasmodium knowlesi parasites at one-month intervals. Clinical data, IgG, IgG1, memory T-cells and monocyte levels were recorded. Results. We observed after three P. knowlesi infections; i) reduced clinical symptoms in all groups with each subsequent infection, ii) increase IgG and IgG1in the malaria control (Pk-only) group iii) increased IgG and IgG1, CD14 + and CD14 - CD16 + in the Schistosoma treated (Schisto/PZQ+Pk) group and iv) significantly lower IgG and IgG1 levels compared to Pk-only, reduced CD4 + CD45RO + and increased CD14 - CD16 + cells in the co-infected (Schisto+Pk) group. Conclusion. Chronic S. mansoni does not compromise establishment of clinical immunity after multiple malaria infections with non-classical monocytes seeming to play a role. Failure to develop robust antibody and memory T-cells may have a long-term impact on acquired immunity to malaria infection.

10-year longitudinal study of malaria in children: Insights into acquisition and maintenance of naturally acquired immunity

Background: Studies of long-term malaria cohorts have provided essential insights into how Plasmodium falciparum interacts with humans, and influences the development of antimalarial immunity. Immunity to malaria is acquired gradually after multiple infections, some of which present with clinical symptoms. However, there is considerable variation in the number of clinical episodes experienced by children of the same age within the same cohort. Understanding this variation in clinical symptoms and how it relates to the development of naturally acquired immunity is crucial in identifying how and when some children stop experiencing further malaria episodes. Where variability in clinical episodes may result from different rates of acquisition of immunity, or from variable exposure to the parasite. Methods: Using data from a longitudinal cohort of children residing in an area of moderate P. falciparum transmission in Kilifi district, Kenya, we fitted cumulative episode curves as monotonic-increasing splines, to 56 children under surveillance for malaria from the age of 5 to 15. Results: There was large variability in the accumulation of numbers of clinical malaria episodes experienced by the children, despite being of similar age and living in the same general location. One group of children from a particular sub-region of the cohort stopped accumulating clinical malaria episodes earlier than other children in the study. Despite lack of further clinical episodes of malaria, these children had higher asymptomatic parasite densities and higher antibody titres to a panel of P. falciparum blood-stage antigens. Conclusions: This suggests development of clinical immunity rather than lack of exposure to the parasite, and supports the view that this immunity to malaria disease is maintained by a greater exposure to P. falciparum, and thus higher parasite burdens. Our study illustrates the complexity of anti-malaria immunity and underscores the need for analyses which can sufficiently reflect the heterogeneity within endemic populations.

Antibody Targets and Properties for Complement-Fixation Against the Circumsporozoite Protein in Malaria Immunity

The Plasmodium falciparum circumsporozoite protein (CSP) forms the basis of leading subunit malaria vaccine candidates. However, the mechanisms and specific targets of immunity are poorly defined. Recent findings suggest that antibody-mediated complement-fixation and activation play an important role in immunity. Here, we investigated the regions of CSP targeted by functional complement-fixing antibodies and the antibody properties associated with this activity. We quantified IgG, IgM, and functional complement-fixing antibody responses to different regions of CSP among Kenyan adults naturally exposed to malaria (n=102) and using a series of rabbit vaccination studies. Individuals who acquired functional complement-fixing antibodies had higher IgG, IgM and IgG1 and IgG3 to CSP. Acquired complement-fixing antibodies targeted the N-terminal, central-repeat, and C-terminal regions of CSP, and positive responders had greater antibody breadth compared to those who were negative for complement-fixing antibodies (p<0.05). Using rabbit vaccinations as a model, we confirmed that IgG specific to the central-repeat and non-repeat regions of CSP could effectively fix complement. However, vaccination with near full length CSP in rabbits poorly induced antibodies to the N-terminal region compared to naturally-acquired immunity in humans. Poor induction of N-terminal antibodies was also observed in a vaccination study performed in mice. IgG and IgM to all three regions of CSP play a role in mediating complement-fixation, which has important implications for malaria vaccine development.

What is the impact of acquired immunity on the transmission of schistosomiasis and the efficacy of current and planned mass drug administration programmes?

Schistosomiasis causes severe morbidity in many countries with endemic infection with the schistosome digenean parasites in Africa and Asia. To control and eliminate the disease resulting from infection, regular mass drug administration (MDA) is used, with a focus on school-aged children (SAC; 5–14 years of age). In some high transmission settings, the World Health Organization (WHO) also recommends the inclusion of at-risk adults in MDA treatment programmes. The question of whether ecology (age-dependant exposure) or immunity (resistance to reinfection), or some combination of both, determines the form of observed convex age-intensity profile is still unresolved, but there is a growing body of evidence that the human hosts acquire some partial level of immunity after a long period of repeated exposure to infection. In the majority of past research modelling schistosome transmission and the impact of MDA programmes, the effect of acquired immunity has not been taken into account. Past work has been based on the assumption that age-related contact rates generate convex horizontal age-intensity profiles. In this paper, we use an individual based stochastic model of transmission and MDA impact to explore the effect of acquired immunity in defined MDA programmes. Compared with scenarios with no immunity, we find that acquired immunity makes the MDA programme less effective with a slower decrease in the prevalence of infection. Therefore, the time to achieve morbidity control and elimination as a public health problem is longer than predicted by models with just age-related exposure and no build-up of immunity. The level of impact depends on the baseline prevalence prior to treatment (the magnitude of the basic reproductive number R0) and the treatment frequency, among other factors. We find that immunity has a larger impact within moderate to high transmission settings such that it is very unlikely to achieve morbidity and transmission control employing current MDA programmes.