Human leukocyte antigen alleles associate with COVID-19 vaccine immunogenicity and risk of breakthrough infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine immunogenicity varies between individuals, and immune responses correlate with vaccine efficacy. Using data from 1,076 participants enrolled in ChAdOx1 nCov-19 vaccine efficacy trials in the United Kingdom, we found that inter-individual variation in normalized antibody responses against SARS-CoV-2 spike and its receptor-binding domain (RBD) at 28 days after first vaccination shows genome-wide significant association with major histocompatibility complex (MHC) class II alleles. The most statistically significant association with higher levels of anti-RBD antibody was HLA-DQB1*06 (P = 3.2 × 10-9), which we replicated in 1,677 additional vaccinees. Individuals carrying HLA-DQB1*06 alleles were less likely to experience PCR-confirmed breakthrough infection during the ancestral SARS-CoV-2 virus and subsequent Alpha variant waves compared to non-carriers (hazard ratio = 0.63, 0.42-0.93, P = 0.02). We identified a distinct spike-derived peptide that is predicted to bind differentially to HLA-DQB1*06 compared to other similar alleles, and we found evidence of increased spike-specific memory B cell responses in HLA-DQB1*06 carriers at 84 days after first vaccination. Our results demonstrate association of HLA type with Coronavirus Disease 2019 (COVID-19) vaccine antibody response and risk of breakthrough infection, with implications for future vaccine design and implementation.

A Rickettsiella Endosymbiont Is a Potential Source of Essential B-Vitamins for the Poultry Red Mite, Dermanyssus gallinae.

Many obligate blood-sucking arthropods rely on symbiotic bacteria to provision essential B vitamins that are either missing or at sub-optimal levels in their nutritionally challenging blood diet. The poultry red mite Dermanyssus gallinae, an obligate blood-feeding ectoparasite, is a serious threat to the hen egg industry. Poultry red mite infestation has a major impact on hen health and welfare and causes a significant reduction in both egg quality and production. Thus far, the identity and biological role of nutrient provisioning bacterial mutualists from D. gallinae are little understood. Here, we demonstrate that an obligate intracellular bacterium of the Rickettsiella genus is detected in D. gallinae mites collected from 63 sites (from 15 countries) across Europe. In addition, we report the genome sequence of Rickettsiella from D. gallinae (Rickettsiella - D. gallinae endosymbiont; Rickettsiella DGE). Rickettsiella DGE has a circular 1.89Mbp genome that encodes 1,973 proteins. Phylogenetic analysis confirms the placement of Rickettsiella DGE within the Rickettsiella genus, related to a facultative endosymbiont from the pea aphid and Coxiella-like endosymbionts (CLEs) from blood feeding ticks. Analysis of the Rickettsiella DGE genome reveals that many protein-coding sequences are either pseudogenized or lost, but Rickettsiella DGE has retained several B vitamin biosynthesis pathways, suggesting the importance of these pathways in evolution of a nutritional symbiosis with D. gallinae. In silico metabolic pathway reconstruction revealed that Rickettsiella DGE is unable to synthesize protein amino acids and, therefore, amino acids are potentially provisioned by the host. In contrast, Rickettsiella DGE retains biosynthetic pathways for B vitamins: thiamine (vitamin B1) via the salvage pathway; riboflavin (vitamin B2) and pyridoxine (vitamin B6) and the cofactors: flavin adenine dinucleotide (FAD) and coenzyme A (CoA) that likely provision these nutrients to the host.

Phylogenetic Inference Using Cytochrome C Oxidase Subunit I (COI) in the Poultry Red Mite, Dermanyssus gallinae in the United Kingdom Relative to a European Framework.

The poultry red mite (Dermanyssus gallinae), an obligatory blood feeding ectoparasite, is primarily associated with laying hens where it is estimated to cause losses of ~€231 million per annum to European farmers. Moderate to high infestation levels result in negative impacts on hen welfare, including increased cannibalism, irritation, feather pecking, restlessness, anemia, and mortality. Acaricides are currently the prevailing method of population control for D. gallinae, although resistance against some classes of acaricide has been widely reported. The development of resistance highlights a growing need for research into alternative control methods, including the development of a suitable and effective vaccine. Understanding the genetic structure of D. gallinae populations can support improved management of acaricide resistance and sustainability of future vaccines, but limited data are currently available. The aim of this study was to characterize D. gallinae isolates from Europe, targeting the cytochrome c oxidase subunit 1 (COI) gene to gain an insight into population structure and genetic diversity of currently circulating mites. Dermanyssus gallinae isolates were collected from Albania, Belgium, Croatia, Czech Republic, Denmark, France, Greece, Italy, the Netherlands, Portugal, Romania, Slovenia, Turkey and the United Kingdom. Genomic DNA was extracted from individual adult D. gallinae mites and a 681bp fragment of the COI gene was amplified and sequenced. Phylogenetic analyses of 195 COI sequences confirmed the presence of multiple lineages across Europe with 76 distinct haplotypes split across three main haplogroups and six sub-haplogroups. Importantly there is considerable inter- and intra-country variation across Europe, which could result from the movement of poultry or transfer of contaminated equipment and/or materials and husbandry practices.

Identification and geographical distribution of pyrethroid resistance mutations in the poultry red mite Dermanyssus gallinae.

BACKGROUND: The poultry red mite (PRM) Dermanyssus gallinae is the most common ectoparasite on poultry and causes high economic losses in poultry farming worldwide. Pyrethroid acaricides have been widely used for its control and, consequently, pyrethroid resistance has arisen. In this study we aim to investigate the occurrence of resistance and study the geographical distribution of pyrethroid resistance mutations across PRM populations in Europe. RESULTS: Full dose-response contact bioassays revealed very high levels of resistance against several pyrethroids (α-cypermethrin, fluvalinate, and cyfluthrin) in two PRM populations from Greece, compared to a susceptible reference strain. Resistance was associated with mutations in the gene encoding the target site of pyrethroids, the voltage-gated sodium channel (VGSC). Mutations, M918L and L925V in domain IIS4-S5 and F1534L in domain IIIS6, were found at positions known to play a role in pyrethroid resistance in other arthropod species. Subsequent screening by sequencing VGSC gene fragments IIS4-S5 and IIIS6 revealed the presence and distribution of these mutations in many European populations. In some populations, we identified additional or different mutations including M918V/T, L925M, T929I, I936F, and F1538L. The latter mutation is a possible alternative for F1538I that has been previously associated with pyrethroid resistance in other Acari species. CONCLUSION: We report very high levels of pyrethroid resistance in PRM populations from Greece, as well as the identification and geographical distribution of 10 pyrethroid resistance mutations in PRM populations across Europe. Our results draw attention to the need for an evidence-based implementation of PRM control, taking acaricide resistance management into consideration. © 2019 Society of Chemical Industry.

Evaluation of vaccine delivery systems for inducing long-lived antibody responses to Dermanyssus gallinae antigen in laying hens.

Dermanyssus gallinae, the poultry red mite, is a global threat to the commercial egg-laying industry. Control of D. gallinae is difficult, with only a limited number of effective pesticides and non-chemical treatments available. Here, we characterize the candidate vaccine antigen D. gallinae cathepsin D-1 (Dg-CatD-1) and demonstrate that purified refolded recombinant Dg-Cat-D1 (rDg-CatD-1) is an active aspartyl proteinase which digests haemoglobin with a pH optimum of pH 4. Soluble protein extracts from D. gallinae also have haemoglobinase activity, with a pH optimum comparable to the recombinant protein, and both proteinase activities were inhibited by the aspartyl proteinase inhibitor Pepstatin A. Enzyme activity and the ubiquitous localization of Dg-CatD-1 protein in sections of adult female mites is consistent with Dg-CatD-1 being a lysosomal proteinase. Using Dg-CatD-1 as a model vaccine antigen, we compared vaccine delivery methods in laying hens via vaccination with: (i) purified rDg-CatD-1 with Montanide™ ISA 71 VG adjuvant; (ii) recombinant DNA vaccines for expression of rDg-CatD-1 and (iii) transgenic coccidial parasite Eimeria tenella expressing rDg-CatD-1. In two independent trials, only birds vaccinated with rDg-CatD-1 with Montanide™ ISA 71 VG produced a strong and long-lasting serum anti-rDg-Cat-D1 IgY response, which was significantly higher than that in control birds vaccinated with adjuvant only. Furthermore, we showed that egg-laying rates of D. gallinae mites fed on birds vaccinated with rDg-CatD-1 in Montanide™ ISA 71 VG was reduced significantly compared with mites fed on unvaccinated birds. RESEARCH HIGHLIGHTS Dermanyssus gallinae cathepsin D-1 (Dg-CatD-1) digests haemoglobin Vaccination of hens with rDg-CatD-1 in Montanide™ ISA 71 VG results in long-lasting IgY levels Serum anti-rDg-CatD-1 antibodies reduce egg laying in D. gallinae after a single blood meal.