Optimal combinations of broadly neutralizing antibodies for prevention and treatment of HIV-1 clade C infection.

CAPRISA, 2016.Abstract available in PDF file

Features of recently transmitted HIV-1 clade C viruses that impact antibody recognition : implications for active and passive immunization.

CAPRISA, 2016.Abstract available in PDF file

An Evaluation of the Effectiveness of Science Field Trips and Hands-On Classroom Activities

This report presents an evaluation of the effectiveness of science field trips and hands-on classroom activities offered and coordinated by the Maria Mitchell Association (MMA). Through our analysis of focus groups, interviews, observations, and surveys, we conclude that the programs are effective in meeting the goals of local teachers. Nevertheless, we make several recommendations, including the implementation of a teacher-provider summit and other professional development activities. We developed a quick and easy evaluation tool for the MMA to gauge the relative success of future field trips and to identify how to improve them

Employing Template-Directed Assembly to Create a Novel Coagulation Assay

Blood coagulation is an important aspect of hemostasis in the human body. Under normal circumstances, the blood coagulates using two different pathways, the intrinsic and the extrinsic. The extrinsic pathway works to counteract trauma but may lead to stroke forming clots. Components for an assay were created so that an assay could be designed to test the functionality of the proteins involved in the clotting cascade: Tissue Factor, factor VII, and factor X when used in conjunction with Template Directed Assembly (TDA) on a nickel-nitriloacetic acid (Ni-NTA) derived liposome

MPI exhibited by single bnAbs and bnAb combinations.

<p>The observed MPI for single bnAbs (A) and predicted MPI values for 2, 3 and 4 bnAb combinations (B-D) are shown. Vertical lines indicate each of the 200 panel viruses and are ordered by MPI values for CAP256-VRC26.25 in all panels. For each virus, the MPI for a bnAb or a bnAb combination is represented by a symbol as shown to the right. The percentage of viruses with MPI <95% for each bnAb and bnAb combination is also indicated.</p

BH predicted IC₈₀ potency-breadth curves scores for all candidate 2, 3 and 4 bnAb combinations against the clade C virus panel.

<p>Potency-breadth curves for all candidate 2 (A), 3 (B) and 4 (C) bnAb combinations are shown for a total of 1,622 bnAb combinations (81 double-, 431 triple-, 1,110 quadruple-bnAb combinations), using BH model predicted IC₈₀ scores. Each combination’s potency-breadth curve is color coded according to the number of bnAbs of different specificities in the combination, e.g. all 4-bnAb combinations that had two V2g bnAbs, and 1 each of other specificities, were assigned to the same category and were color coded blue in (C). The best-in-category bnAb combinations are highlighted in darker colors in A-C, and the others are shown by matched lighter colors. In (B) and (C), “0/1” indicates combinations in which the indicated epitope may or may not have been covered by a representative bnAb. Combinations with a given total number of bnAbs that have 2 bnAbs targeting a single epitope and up to one bnAb targeting other epitopes were grouped together into categories. Such categories are represented as e.g. “2 CD4bs + 0/1 V2g + 0/1V3g + 0/1 MPER” in the figure, which in the case of 4 bnAb combinations, are composed of combination types “2 CD4bs + V2g + V3g”, “2CD4bs + V2g + MPER” and “2CD4bs + V3g + MPER.</p

Extent of neutralization by multiple active bnAbs from best-in-category combinations.

<p>Modified IC₈₀ potency-breadth curves are shown for best-in-category 2, 3, and 4 bnAb combinations. These modified curves measure the fraction of all 200 viruses that are neutralized at predicted combination IC₈₀ values, but limited by counting only those viruses that were simultaneously neutralized by at least 1, 2 or 3 bnAbs in the combination. Potency-breadth curves are shown for the best 2 bnAb combinations in which at least 1 or 2 bnAbs were required to be simultaneously active at IC₈₀ thresholds of <1 μg/ml, 5 μg/ml or 10 μg/ml (A). Similar potency-breadth curves are shown for the best 3 bnAb (B) or 4 bnAb (C) combinations in which at least 2 or 3 bnAbs were required to be simultaneously active at these IC₈₀ thresholds. The modified potency-breadth curves in this figure do not reach the indicated IC₈₀ thresholds when 2 or more bnAbs are required to be active because the curves are driven by the IC₈₀ value of the more potent active bnAb in the combination, which is often much lower than the activity threshold IC80.</p

Comparison of best-in-category bnAb combinations for potency and breadth of neutralization.

<p>Comparisons of best combinations from each category within the 2- (A-C), 3- (D-F) and 4- (G-I) bnAb combinations are presented. Shown below each combination are its geometric mean and median IC₈₀ titer and the percent viral coverage at IC₈₀ < 10 μg/ml (A, D, G). Combinations are ordered using geometric mean IC₈₀ titers, and a combination is indicated as better than (‘>‘) the proceeding combination when the difference in geometric mean IC₈₀ exceeded 0.001 μg/ml, otherwise it is indicated as similar (‘~’). The distributions of IC₈₀ scores for the best combinations were compared using a Wilcoxon Rank Sum Test, and only those p-values with q-value < 0.1 are shown. Potency-breadth curves (B, E, H) and distributions of IC₈₀ values (C, F, I) for the top 2 combinations are shown. Grey lines in C, F, I connect the predicted IC₈₀ values for the same virus.</p

Neutralization activity of bnAbs against clade C virus panel.

<p>Potency-breadth curves are presented for both IC₅₀ (A) and IC₈₀ (B) titers. BnAbs are color coded and grouped by target epitopes. Bold lines indicate bnAbs that were best in class for V2-glycan (V2g), V3-glycan (V3g), CD4bs, and MPER epitopes. Dashed vertical lines indicated the lowest and highest concentration tested. Neutralization data are also presented as scatter plots of IC₅₀ (C) and IC₈₀ (D) titers in which each virus is represented by an individual dot. The highest concentration tested for each bnAb and the percentage of viruses neutralized are indicated. Solid bars represent median titers. Heat maps of IC₅₀ (E) and IC₈₀ (F) were generated using the Heatmap tool on the Los Alamos HIV Database. In the heatmaps, rows represent viruses, and columns represent bnAbs. The darker hues indicate more potent neutralization, and blue (for contrast) indicates the virus had IC₅₀ or IC₈₀ above threshold, unable to reach this level of neutralization at the highest concentration of bnAb tested. The order of viruses is same in panels E and F.</p