A Glycolipid Adjuvant, 7DW8-5, Enhances CD8+ T Cell Responses Induced by an Adenovirus-Vectored Malaria Vaccine in Non-Human Primates

A key strategy to a successful vaccine against malaria is to identify and develop new adjuvants that can enhance T-cell responses and improve protective immunity. Upon co-administration with a rodent malaria vaccine in mice, 7DW8-5, a recently identified novel analog of α-galactosylceramide (α-GalCer), enhances the level of malaria-specific protective immune responses more strongly than the parent compound. In this study, we sought to determine whether 7DW8-5 could provide a similar potent adjuvant effect on a candidate human malaria vaccine in the more relevant non-human primate (NHP) model, prior to committing to clinical development. The candidate human malaria vaccine, AdPfCA (NMRC-M3V-Ad-PfCA), consists of two non-replicating recombinant adenoviral (Ad) vectors, one expressing the circumsporozoite protein (CSP) and another expressing the apical membrane antigen-1 (AMA1) of Plasmodium falciparum. In several phase 1 clinical trials, AdPfCA was well tolerated and demonstrated immunogenicity for both humoral and cell-mediated responses. In the study described herein, 25 rhesus macaques received prime and boost intramuscular (IM) immunizations of AdPfCA alone or with an ascending dose of 7DW8-5. Our results indicate that 7DW8-5 is safe and well-tolerated and provides a significant enhancement (up to 9-fold) in malaria-specific CD8+ T-cell responses after both priming and boosting phases, supporting further clinical development.     

Anthropogenic and Natural Disturbance Differentially Affect Sagebrush Bird Habitat Use

North American sagebrush (Artemisia spp.)-obligate birds are experiencing steep population declines due in part to increased disturbance, mainly human-caused, across their range. At the eastern edge of the sagebrush steppe, this issue may potentially be exacerbated because of natural disturbance by black-tailed prairie dogs (Cynomys ludovicianus). Our goal was to compare local and landscape models of habitat use by greater sage-grouse (Centrocercus urophasianus), Brewer's sparrow (Spizella breweri), and sage thrasher (Oreoscoptes montanus) with models including effects of natural (i.e., prairie dog) and anthropogenic disturbance. We used a combination of field data collection, and state and national datasets for the Thunder Basin National Grassland, eastern Wyoming, USA, to understand the factors that influence lek attendance by sage-grouse and habitat use by 2 passerines in this system. For all 3 species, models including big sagebrush (Artemisia tridentata) cover at local and landscape scales were the most competitive among univariate models, supporting the paradigm that sagebrush is key for these species. Models including anthropogenic disturbance (well density, road density) explained more variation than models of prairie dog disturbance alone for 2 of the 3 species, but long-term disturbance by prairie dogs did reduce abundance of Brewer's sparrows. Although long-term prairie dog disturbance has the potential to reduce sagebrush cover for sagebrush-obligate birds, such events are likely rare because outbreaks of plague (Yersina pestis) and lethal control on borders with private land reduce prairie dog disturbance. Conversely, anthropogenic disturbance is slated to increase in this system, suggesting potentially accelerated declines for sagebrush birds into the future. © 2020 The Wildlife Society.     

Elotuzumab directly enhances NK cell cytotoxicity against myeloma via CS1 ligation: evidence for augmented NK cell function complementing ADCC

Elotuzumab is a monoclonal antibody in development for multiple myeloma (MM) that targets CS1, a cell surface glycoprotein expressed on MM cells. In preclinical models, elotuzumab exerts anti-MM efficacy via natural killer (NK)-cell-mediated antibody-dependent cellular cytotoxicity (ADCC). CS1 is also expressed at lower levels on NK cells where it acts as an activating receptor. We hypothesized that elotuzumab may have additional mechanisms of action via ligation of CS1 on NK cells that complement ADCC activity. Herein, we show that elotuzumab appears to induce activation of NK cells by binding to NK cell CS1 which promotes cytotoxicity against CS1(+) MM cells but not against autologous CS1(+) NK cells. Elotuzumab may also promote CS1–CS1 interactions between NK cells and CS1(+) target cells to enhance cytotoxicity in a manner independent of ADCC. NK cell activation appears dependent on differential expression of the signaling intermediary EAT-2 which is present in NK cells but absent in primary, human MM cells. Taken together, these data suggest elotuzumab may enhance NK cell function directly and confer anti-MM efficacy by means beyond ADCC alone.     

Maternal coding variants in complement receptor 1 and spontaneous idiopathic preterm birth

Preterm birth (PTB) is a major global public health concern. However, little is known about the pathophysiology of spontaneous idiopathic PTB. We tested the hypothesis that rare variants in families would target specific genes and pathways that contribute to PTB risk in the general population. Whole-exome sequencing was performed on 10 PTB mothers from densely affected families including two mother–daughter pairs. We identified novel variants shared between the two mother–daughter pairs when compared to a 1000 Genomes Project background exome file and investigated these genes for pathway aggregation using the Kyoto Encyclopedia of Genes and Genomes (KEGG). Genes in enriched pathways were then surveyed in the other six PTB exomes and tested for association in a larger number of nuclear families. The KEGG complement and coagulation cascade was one of the most enriched pathways in our two mother–daughter pairs. When the six genes found in this pathway (CFH, CR1, F13B, F5, CR2, and C4BPA) were examined for novel missense variants, half of all the exomes harbored at least one. Association analysis of variants in these six gene regions in nuclear families from Finland (237 cases and 328 controls) found statistically significant associations after multiple test corrections in three CR1 SNPs; the strongest in an exonic missense SNP, rs6691117, p value = 6.91e?5, OR = 1.71. Our results demonstrate the importance of the complement and coagulation cascades in the pathophysiology of PTB, and suggest potential screening and intervention approaches to prevent prematurity that target this pathway.     

ON THE BREEDING OF THE WHITE-RUMPED SWIFT (APUS CAFFER CAFFER) IN GATOOMA

Crawford, R. J. M., Cooper, J. &; Shelton, P. A. 1982. Distribution, population size, breeding and conservation of the Kelp Gull in southern Africa. Ostrich 53:164:177.

The Kelp Gull Lams dominicanus in Africa occurs coastally between Luanda, Angola and Delagoa Bay, Moçmbique. It breeds between Cape Cross Lagoon, South West Africa/Namibia and Riet River, eastern Cape, South Africa. Censuses of nests and breeding birds at all known southern African breeding localities in the period 1976–1981 indicated that 11 199 pairs bred at 52 localities; 79.5% of this population occurred in South Africa, 57,1% in the Saldanha Bay to Dassen Island region, southwestern Cape. Of the breeding pairs 83% occurred on offshore islands and rocks. Colony size at islands is related to their surface area andMayalso be influenced by food availability and the level of human disturbance. The species breeds in a wide variety of habitats ranging from cliffs and rock stacks to wooden platforms, lowlying vegetation among sand dunes and estuarine sandbars. Any available material is used in the construction of nests, whichMaybe as dense as 4/m² Clutch size is 2–3 eggs. In 1978 breeding took place earlier in South Africa than in South West Africa/Namibia. 92% of the population breeds m sites which are legally protected. Kelp Gulls have decreased or increased in numbers at some breeding localities but there is no clear overall trend. Any increases in colony size near urban areasMayresult in added airstrike hazards.     

Breeding distribution,population size and conservation of the Greyheaded Gull Larus cirrocephalus in southern Africa

Brooke, R.K., Allan, D.G., Cooper, J., Cyrus, D.P., Dean, W.R.J., Dyer, B.M., Martin, A.P. & Taylor, R.H. 1999. Breeding distribution, population size and conservation of the Greyheaded Gull Larus cirrocephalus in southern Africa. Ostrich 70 (3&4): 157–163.

The Greyheaded Gull Larus cirrocephalus occurs throughout southern Africa, both coastally and inland, and has bred at one time or another at 67 known localities since the 1860s. Most of these sites have been occupied by small numbers of birds, even single pairs, and for only one or a few years. The two principal breeding areas are the East Rand in Gauteng and Lake St Lucia in KwaZulu-Natal, both in South Africa. The next most important sites are Walvis Bay, Namibia and Lake Ngami, Botswana. The total southern African breeding population is estimated as about 2000 pairs. The Greyheaded Gull is not a threatened species in southern Africa, with 27 breeding sites supporting more than half the breeding population within formally conserved areas.