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. 2018 Jun 18;9:2363. doi: 10.1038/s41467-018-04758-9

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© The Author(s) 2018

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 4 — SHIV-C5 challenges and duration of protective immune responses. a Monkeys were immunized with either human serum albumin (Group 1) or gp120 glycoproteins corresponding to the Envs of the transmitted/founder virus and sequential virus isolates (at weeks 53, 78 and 100) from an HIV-1_CH505-infected individual (Groups 2 and 3) (green). Immunized monkeys were challenged with SHIV-C5 mixed with BNM-III-170 (Groups 1 and 3) or DMSO (Group 2) (blue). To accommodate the complete study in this schematic diagram, the time intervals on the horizontal axis are approximated. b Kaplan–Meier curves show the percentage of the monkeys in each group that remained uninfected after three high-dose intrarectal challenges with the heterologous Tier-2/3 transmitted/founder SHIV-C5³⁹. The monkeys were boosted with human serum albumin (HSA) (Group 1) or HIV-1_CH505 gp120 (Groups 2 and 3) either two weeks (Challenges 1 and 2) or four weeks (Challenge 3) before the SHIV-C5 challenge. Infection of the Group 2 monkeys occurred at a rate expected for naive monkeys challenged with the same dose (3.5 animal infectious dose (AID₅₀) units) of SHIV-C5^{39, 42}. The indicated P values were obtained using the log rank test (ns, not significant). The rate of infection of the Group 3 monkeys was significantly lower than that expected if gp120 immunization and BNM-III-170 treatment were simply additive (P = 0.0186, log rank test). c The results of the three SHIV-C5 challenges shown in (b) were used to calculate the infection rate, which is the number of infections/number of exposures. Compared with unvaccinated historical controls³⁹, the Jewell bias-corrected relative risk of SHIV-C5 acquisition in the Group 2 monkeys is 0.95 ± 0.24 (95% confidence interval). d The percentage of Group 3 monkeys that remained uninfected after SHIV-C5 challenges at different times following the last gp120 immunization is shown. The green bars indicate SHIV-C5 challenges that were conducted in the presence of BNM-III-170 (300 μM) and the magenta bar indicates a SHIV-C5 challenge performed in the absence of BNM-III-170. Each of the values obtained with BNM-III-170 significantly differs from that obtained in the absence of the CD4mc (P < 0.05, one-tailed Fisher exact probability test). The values obtained for the SHIV-C5 challenges performed with BNM-III-170 (green bars) do not significantly differ from each other