Establishment of a Poliovirus Containment Program and Containment Certification Process for Poliovirus-Essential Facilities, United States 2017-2022.

Upon declaration of poliovirus (PV) type 2 eradication in 2015, the World Health Organization (WHO) published PV containment requirements in the Global Action Plan III (GAPIII) for mitigating the risk of a facility-associated release post eradication. In 2018, the 71st World Health Assembly resolution urged member states retaining PV to appoint a National Authority for Containment (NAC), reduce the number of PV facilities, and submit applications for containment certification. The United States (US) NAC was established in 2018 for containment oversight, and two paths to WHO GAPIII containment certification were developed. Facilities retaining PV were identified through national poliovirus containment surveys. The US NAC conducted 27 site visits at 18 facilities (20 laboratories: A/BSL-2 (65%), A/BSL-3 (20%), and storage-only (15%)) to verify the implementation of US NAC's preliminary containment measures. The NAC identified areas for improvement in seven categories: primary containment, decontamination, hand hygiene, security, emergency response, training, and immunization practices. Sixteen facility applications were endorsed to pursue poliovirus-essential facility (PEF) certification, whereas four facilities opted to withdraw during the containment certification process. The US made noteworthy progress in PV containment to enhance biosafety and biosecurity practices at US PV facilities to safeguard the polio eradication effort.

Novel QTLs for HDL levels identified in mice by controlling for Apoa2 allelic effects: confirmation of a chromosome 6 locus in a congenic strain.

Atherosclerosis is a complex disease resulting from the interaction of multiple genes, including those causing dyslipidemia. Relatively few of the causative genes have been identified. Previously, we identified Apoa2 as a major determinant of high-density lipoprotein cholesterol (HDL-C) levels in the mouse model. To identify additional HDL-C level quantitative trait loci (QTLs), while controlling for the effect of the Apoa2 locus, we performed linkage analysis in 179 standard diet-fed F(2) mice derived from strains BALB/cJ and B6.C-H25(c) (a congenic strain carrying the BALB/c Apoa2 allele). Three significant QTLs and one suggestive locus were identified. A female-specific locus mapping to chromosome 6 (Chr 6) also exhibited effects on plasma non-HDL-C, apolipoprotein AII (apoAII), apoB, and apoE levels. A Chr 6 QTL was independently isolated in a related congenic strain (C57BL/6J vs. B6.NODc6: P = 0.003 and P = 0.0001 for HDL-C and non-HDL-C levels, respectively). These data are consistent with polygenic inheritance of HDL-C levels in the mouse model and provide candidate loci for HDL-C and non-HDL-C level determination in humans.

Immediate early effector functions of virus-specific CD8+CCR7+ memory cells in humans defined by HLA and CC chemokine ligand 19 tetramers.

Memory T cells exhibit a high degree of heterogeneity in terms of their phenotype and functional characteristics. It has been proposed that the CCR7 chemokine receptor divides memory T cell populations into central memory T cells and effector memory T cells with distinct functions in secondary immune responses. We were interested whether this hypothesis holds true in experiments performed on Ag-specific CD8(+) T cells. To identify CCR7(+) cells, we engineered a fluorescent ligand for CCR7; results with the new CC chemokine ligand 19 chemotetramer were verified by staining with a CCR7 mAb. Staining with the CC chemokine ligand 19 chemotetramer reveals two subsets within CCR7(+) cells: a CCR7(int) population containing memory cells and a CCR7(high) population containing naive T cells. Phenotypic analysis of MHC class I/peptide tetramer-positive cells revealed that HLA-A2-restricted CMV-specific CD8 T cells exhibit the lowest percentage of CCR7(+) cells (0.5-5%), while HLA-A2-restricted flu- and HLA-B8-restricted EBV-specific CD8 T cells showed the highest (45-70%). Intracellular staining of unstimulated cells revealed that both CCR7(int)- and CCR7(-)-specific CD8 T cells exhibit a detectable level of perforin. Both CCR7(int) and CCR7(-) Ag-specific CD8(+) T cells produced IFN-gamma and TNF-alpha following short-term peptide stimulation. Therefore, our finding that CCR7(+)CD8(+) T cells are able to exert immediate effector functions requires a substantial revision to the central and effector memory hypothesis.