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Live, attenuated viral vectors that express HIV-1 antigens are being investigated as an approach to generating durable immune responses against HIV-1 in humans. We recently developed a replication-competent, highly attenuated Ad26 vector that expresses mosaic HIV-1 Env (rcAd26.MOS1.HIV-Env, \"rcAd26\"). Here we present the results of a first-in-human, placebo-controlled clinical trial to test the safety, immunogenicity and mucosal shedding of rcAd26 given orally. Healthy adults were randomly assigned to receive a single oral dose of vaccine or placebo at 5:1 ratio in a dosage escalation of 10^8 to 10^11 rcAd26 VP (nominal doses) at University of Rochester Medical Center, Rochester, NY, USA. Participants were isolated and monitored for reactogenicity for 10 days post-vaccination, and adverse events were recorded up to day 112. Rectal and oropharyngeal secretions were evaluated for shedding of the vaccine. Humoral and cellular immune responses were measured. Household contacts were monitored for secondary vaccine transmission. We enrolled 22 participants and 11 household contacts between February 7 and June 24, 2015. 18 participants received one dose of HIV-1 vaccine and 4 participants received placebo. The vaccine caused only mild to moderate adverse events. No vaccine-related SAEs were observed. No infectious rcAd26 viral particles were detected in rectal or oropharyngeal secretions from any participant. Env-specific ELISA and ELISPOT responses were undetectable. No household contacts developed vaccine-induced HIV-1 seropositivity or vaccine-associated illness. The highly attenuated rcAd26.MOS1.HIV-Env vaccine was well tolerated up to 10^11 VP in healthy, HIV-1-uninfected adults, though the single dose was poorly immunogenic suggesting the replicative capacity of the vector was too attenuated. There was no evidence of shedding of infectious virus or secondary vaccine transmission following the isolation period. These data suggest the use of less attenuated viral vectors in future studies of live, oral HIV-1 vaccines. ClinicalTrials.gov NCT02366013.

Background. We report the first-in-human safety and immunogenicity assessment of a prototype intranasally administered, replication-competent Sendai virus (SeV)–vectored, human immunodeficiency virus type 1 (HIV-1) vaccine. Methods. Sixty-five HIV-1–uninfected adults in Kenya, Rwanda, and the United Kingdom were assigned to receive 1 of 4 prime-boost regimens (administered at 0 and 4 months, respectively; ratio of vaccine to placebo recipients, 12:4): priming with a lower-dose SeV-Gag given intranasally, followed by boosting with an adenovirus 35–vectored vaccine encoding HIV-1 Gag, reverse transcriptase, integrase, and Nef (Ad35-GRIN) given intramuscularly (SLA); priming with a higher-dose SeV-Gag given intranasally, followed by boosting with Ad35-GRIN given intramuscularly (SHA); priming with Ad35-GRIN given intramuscularly, followed by boosting with a higher-dose SeV-Gag given intranasally (ASH); and priming and boosting with a higher-dose SeV-Gag given intranasally (SHSH). Results. All vaccine regimens were well tolerated. Gag-specific IFN-γ enzyme-linked immunospot–determined response rates and geometric mean responses were higher (96% and 248 spot-forming units, respectively) in groups primed with SeV-Gag and boosted with Ad35-GRIN (SLA and SHA) than those after a single dose of Ad35-GRIN (56% and 54 spot-forming units, respectively) or SeV-Gag (55% and 59 spot-forming units, respectively); responses persisted for ≥8 months after completion of the prime-boost regimen. Functional CD8⁺ T-cell responses with greater breadth, magnitude, and frequency in a viral inhibition assay were also seen in the SLA and SHA groups after Ad35-GRIN boost, compared with those who received either vaccine alone. SeV-Gag did not boost T-cell counts in the ASH group. In contrast, the highest Gag-specific antibody titers were seen in the ASH group. Mucosal antibody responses were sporadic. Conclusions. SeV-Gag primed functional, durable HIV-specific T-cell responses and boosted antibody responses. The prime-boost sequence appears to determine which arm of the immune response is stimulated. Clinical Trials Registration. NCT01705990.

Testing the often-made assumption that ice particle aggregates (snowflakes) are well represented by oblate spheroids, ellipsoid fits are applied to aggregate images. An algorithm to retrieve both the ellipsoidal parameters and the orientations of the fitted ellipsoids is applied to Multi-Angle Snowflake Camera measurements of ice particle aggregates observed in Alaska. The resulting ellipsoids have shapes closer to prolate spheroids than the oft-assumed oblate spheroids. A robust linear relationship exists between the two characteristic aspect ratios of the ellipsoids. The most probable orientation of the maximum dimension of the retrieved ellipsoids is not in the horizontal plane, and the rotational angles of the maximum dimensions in the horizontal plane are not uniform, but instead display some correlation with the wind direction at the times of the measurements. The retrieval results can be used to improve the representation of aggregates in microphysics and/or electromagnetic radiation scattering models applicable to radar and satellite measurements.

Testing the often-made assumption that ice particle aggregates (snowflakes) are well represented by oblate spheroids, ellipsoid fits are applied to aggregate images. An algorithm to retrieve both the ellipsoidal parameters and the orientations of the fitted ellipsoids is applied to Multi-Angle Snowflake Camera measurements of ice particle aggregates observed in Alaska. The resulting ellipsoids have shapes closer to prolate spheroids than the oft-assumed oblate spheroids. A robust linear relationship exists between the two characteristic aspect ratios of the ellipsoids. The most probable orientation of the maximum dimension of the retrieved ellipsoids is not in the horizontal plane, and the rotational angles of the maximum dimensions in the horizontal plane are not uniform, but instead display some correlation with the wind direction at the times of the measurements. Finally, the retrieval results can be used to improve the representation of aggregates in microphysics and/or electromagnetic radiation scattering models applicable to radar and satellite measurements.