Search

Background: Defining mucosal immune responses and inflammation to candidate human immunodeficiency virus type 1 (HIV-1) vaccines represents a current research priority for the HIV-1 vaccine field. In particular, it is unclear whether intramuscular immunization can elicit immune responses at mucosal surfaces in humans., Methods: In this double-blind, randomized, placebo-controlled clinical trial, we evaluated systemic and mucosal immune responses to a candidate adenovirus serotype 26 (Ad26) vectored HIV-1 envelop (Env) vaccine in baseline Ad26-seronegative and Ad26-seropositive healthy volunteers. Systematic mucosal sampling with rectal Weck-Cel sponges and rectal biopsies were performed., Results: Intramuscular immunization elicited both systemic and mucosal Env-specific humoral and cellular immune responses in the majority of subjects. Individuals with preexisting Ad26-specific neutralizing antibodies had vaccine-elicited immune responses comparable to those of subjects who were Ad26 seronegative. We also observed no increase in activated total or vector-specific mucosal CD4+ T lymphocytes following vaccination by either histopathology or flow cytometry., Conclusions: These data demonstrate that a single intramuscular administration of this Ad26-vectored HIV-1 Env vaccine elicited both systemic and mucosal immune responses in humans. Induction of antigen-specific humoral and cellular mucosal immunity was not accompanied by a detectable increase in mucosal inflammation., Clinical Trials Registration: NCT01103687., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: We report the first-in-human safety and immunogenicity assessment of a prototype hexon chimeric adenovirus (Ad) serotype 5 (Ad5) vector containing the hexon hypervariable regions of Ad serotype 48 (Ad48) and expressing human immunodeficiency virus (HIV) type 1 EnvA., Methods: Forty-eight Ad5 and Ad48 seronegative, HIV-uninfected subjects were enrolled in a randomized, double-blind, placebo-controlled, dose escalation phase 1 study. Four groups of 12 subjects received 10(9) to 10(11) viral particles (vp) of the Ad5HVR48.EnvA.01 vaccine (n = 10 per group) or placebo (n = 2 per group) at week 0 or weeks 0, 4, and 24. Safety and immunogenicity were assessed., Results: Self-limited reactogenicity was observed after the initial immunization in the highest (10(11) vp) dose group. Responses in vaccinees included Ad48 neutralizing antibody (nAb) titers higher than Ad5 nAb titers, EnvA-specific enzyme-linked immunosorbent assay titers, and EnvA-specific enzyme-linked immunospot assay responses, and these responses generally persisted at week 52. At week 28 in the 10(9), 10(10), and 10(11) vp 3-dose groups, geometric mean EnvA enzyme-linked immunosorbent assay titers were 5721, 10 929, and 3420, respectively, and Ad48 nAb titers were a median of 1.7-fold higher than for Ad5., Conclusions: Ad5HVR48.ENVA.01 was safe, well tolerated, and immunogenic at all doses tested. Vector-elicited nAb responses were greater for Ad48 than Ad5, confirming that Ad-specific nAbs in humans are primarily, but not exclusively, directed against the hexon hypervariable regions. Clinical Trials Registration. NCT00695877., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Adenovirus serotype 26 (Ad26) has been developed as a novel candidate vaccine vector for human immunodeficiency virus type 1 (HIV-1) and other pathogens. The primary safety and immunogenicity data from the Integrated Preclinical/Clinical AIDS Vaccine Development Program (IPCAVD) 001 trial, the first-in-human evaluation of a prototype Ad26 vector-based vaccine expressing clade A HIV-1 Env (Ad26.ENVA.01), are reported concurrently with this article. Here, we characterize in greater detail the humoral and cellular immune responses elicited by Ad26.ENVA.01 in humans., Methods: Samples from the IPCAVD 001 trial were used for humoral and cellular immunogenicity assays., Results: We observed a dose-dependent expansion of the magnitude, breadth, and epitopic diversity of Env-specific binding antibody responses elicited by this vaccine. Antibody-dependent cell-mediated phagocytosis, virus inhibition, and degranulation functional activity were also observed. Env-specific cellular immune responses induced by the vaccine included multiple CD8(+) and CD4(+) T-lymphocyte memory subpopulations and cytokine secretion phenotypes, although cellular immune breadth was limited. Baseline vector-specific T-lymphocyte responses were common but did not impair Env-specific immune responses in this study., Conclusion: Ad26.ENVA.01 elicited a broad diversity of humoral and cellular immune responses in humans. These data support the further clinical development of Ad26 as a candidate vaccine vector., Clinical Trials Registration: NCT00618605.

Background: We report the first-in-human safety and immunogenicity assessment of a prototype Ad26 vector-based human immunodeficiency virus (HIV) vaccine in humans., Methods: Sixty Ad26-seronegative, healthy, HIV-uninfected subjects were enrolled in a randomized, double-blinded, placebo-controlled, dose-escalation phase 1 study. Five groups of 12 subjects received 10(9)-10(11) vp of the Ad26-EnvA vaccine (N = 10/group) or placebo (N = 2/group) at weeks 0 and 24 or weeks 0, 4, and 24. Safety and immunogenicity were assessed., Results: Self-limited reactogenicity was observed after the initial immunization at the highest (10(11) vp) dose. No product-related SAEs were observed. All subjects who received the Ad26-EnvA vaccine developed Ad26 NAb titers, EnvA-specific enzyme-linked immunosorbent assays (ELISA) titers, and EnvA-specific enzyme-linked immunospot assays (ELISPOT) responses. These responses persisted at week 52. At week 28 in the 10(9), 10(10), 10(11) vp 3-dose and the 10(10) and 5 × 10(10) vp 2-dose groups, geometric mean EnvA ELISA titers were 6113, 12 470, 8545, 3470, and 9655 and mean EnvA ELISPOT responses were 397, 178, 736, 196, and 1311 SFC/10(6) peripheral blood mononuclear cells, respectively., Conclusion: This Ad26 vectored vaccine was generally safe and immunogenic at all doses tested. Reactogenicity was minimal with doses of 5 × 10(10) vp or less. Ad26 is a promising new vaccine vector for HIV-1., Clinical Trials Registration: NCT00618605.

Fattening pigs are often infected with campylobacter. To eliminate campylobacter from the pig population, a top-down approach, involving the breeding and reproduction farms, seems appropriate. In order to investigate the effectiveness of a top-down approach, sows' faeces from the following farms were analysed for the presence of campylobacter: one specific pathogen free (SPF) farm, three top-breeding farms with no connection with SPF breeding, and a breeding farm repopulated with SPF sows after a period of vacancy (farm 5). The faeces samples from the SPF farm were free from campylobacter. The three top-breeding farms provided faeces samples which were 98% positive for campylobacter. However, only 22% of the faeces samples from farm 5 were positive for campylobacter. In a period of 20 months, the percentage of sows infected with campylobacter on farm 5 did not significantly increase. Genetic typing with ERIC-PCR and RFLP of campylobacter isolates from one of the top-breeding farms and from farm 5 showed a high diversity of campylobacter types. The results suggest that a campylobacter-free pig population can be established in breeding farms by combining a top-down approach (campylobacter-free top-breeding farms) with a strict regime of hygiene management.

The excretion of campylobacter by eight individually housed fattening pigs was monitored during 15 weeks. Rectal faeces samples were collected six times from these pigs and twice from their mothers (seven sows). Campylobacter was cultured from these samples on Preston medium. In some pigs, samples positive for campylobacter alternated with negative samples. Campylobacter was detected in at least four of the six samples collected per fattening pig. The average campylobacter count per sampling showed a decreasing trend (P < 0.001). Of the seven sows, six were shown to excrete campylobacter. Campylobacter isolates of pigs and sows were typed using the Enterobacterial Repetitive Intergenic Consensus Polymerase Chain Reaction (ERIC-PCR); 28 different campylobacter types were distinguished. Up to five different types were isolated from single faeces samples. Individual porkers could harbour up to eight types during their fattening period. The three types most frequently isolated from the fattening pigs were also present in the sows.

The campylobacter infection of 10 sows and their piglets was monitored. These pigs were kept on two multiplier farms. Rectal faeces samples were taken from the sows shortly before littering and at different intervals after littering. Swab samples of rectal content were taken from six piglets per sow at different intervals after birth. Nine sows were shown to be infected with campylobacter before litter and all sows after litter, with an average colony count of 4.1 in log N g-1 of faeces. Half of the piglets became infected with campylobacter during the first week of life and 85%, after four weeks. Two genetic subtyping methods (ERIC-PCR and RFLP) were used to study the relationships between campylobacter isolates from sows and piglets. A large diversity of campylobacter subtypes was found. Nevertheless, piglets and their mothers often harboured campylobacter isolates with identical genetic subtyping profiles, suggesting that piglets become infected via their mothers. However, observed similarities in genetic subtyping profiles between campylobacters isolated on different farms made this difficult to prove.