Summary Preclinical studies of HIV-1 vaccine candidates have typically shown post-infection virologic control, but protection against acquisition of infection has previously only been reported against neutralization-sensitive virus challenges1–3. Here we demonstrate vaccine protection against acquisition of fully heterologous, neutralization-resistant virus challenges in rhesus monkeys. Adenovirus/poxvirus and adenovirus/adenovirus vector-based vaccines expressing SIVsmE543 Gag, Pol, and Env antigens resulted in a ≥80% reduction in the per-exposure probability of infection4,5 against repetitive, intrarectal SIVmac251 challenges in rhesus monkeys. Protection against acquisition of infection exhibited distinct immunologic correlates as compared with post-infection virologic control and required the inclusion of Env in the vaccine regimen. These data demonstrate the first proof-of-concept that optimized HIV-1 vaccine candidates can block acquisition of stringent, heterologous, neutralization-resistant virus challenges in rhesus monkeys.

Natural killer (NK) cells have traditionally been considered nonspecific components of innate immunity, but recent studies have shown features of antigen-specific memory in murine NK cells. However, it has remained unclear whether this phenomenon also exists in primates. Compared to NK cells from uninfected macaques, we found splenic and hepatic NK cells from SHIV-SF162P3- and SIVmac251-infected animals specifically lysed Gag- and Env-pulsed dendritic cells (DCs) in an NKG2-dependent fashion. Moreover, splenic and hepatic NK cells from Ad26-vaccinated macaques efficiently lysed antigen-matched but not antigen-mismatched targets 5 years post-vaccination. These data demonstrate that robust, durable, antigen-specific NK cell memory can be induced in primates following both infection and vaccination, and could be important for vaccines against HIV-1 and other pathogens.

Nosocomial infections caused by Staphylococcus epidermidis are characterized by biofilm formation on implanted medical devices. Quorum-sensing regulation plays a major role in the biofilm development of many bacterial pathogens. Here, we describe luxS, a quorum-sensing system in staphylococci that has a significant impact on biofilm development and virulence. We constructed an isogenic ⌬luxS mutant strain of a biofilmforming clinical isolate of S. epidermidis and demonstrated that luxS signaling is functional in S. epidermidis. The mutant strain showed increased biofilm formation in vitro and enhanced virulence in a rat model of biofilm-associated infection. Genetic complementation and addition of autoinducer 2-containing culture filtrate restored the wild-type phenotype, demonstrating that luxS repressed biofilm formation through a cell-cell signaling mechanism based on autoinducer 2 secretion. Enhanced production of the biofilm exopolysaccharide polysaccharide intercellular adhesin in the mutant strain is presumably the major cause of the observed phenotype. The agr quorum-sensing system has previously been shown to impact biofilm development and biofilm-associated infection in a way similar to that of luxS, although by regulation of different factors. Our study indicates a general scheme of quorum-sensing regulation of biofilm development in staphylococci, which contrasts with that observed in many other bacterial pathogens.

The earliest events following mucosal HIV-1 infection, prior to measurable viremia, remain poorly understood. Here we show by detailed necropsy studies that the virus can disseminate rapidly following mucosal SIV infection of rhesus monkeys and trigger components of the inflammasome, both at the site of inoculation and at early sites of distal virus spread. By 24 hours following inoculation, a proinflammatory signature that lacked antiviral restriction factors was observed in viral RNA positive tissues. The early innate response included expression of NLRX1, which inhibits antiviral responses, and activation of the TGF-β pathway, which negatively regulates adaptive immune responses. These data suggest a model in which the virus triggers specific host mechanisms that suppress the generation of antiviral innate and adaptive immune responses in the first few days of infection, thus facilitating its own replication. These findings have important implications for the development of vaccines and other strategies to prevent infection.

Here, we describe a simple method to prepare oil-repellent surfaces with inherent reactivity. Liquid-like copolymers with pendant reactive groups are covalently immobilized onto substrates via a sequential layer-by-layer method. The stable and transparent nanocoatings showed oil repellency to a broad range of organic liquids even in the presence of reactive sites. Functional molecules could be covalently immobilized onto the oil-repellent surfaces. Moreover, the liquid repellency can be maintained or finely tailored after post-chemical modification via synergically tailoring the film thickness, selection of capping molecules, and labeling degree of the capping molecules. Oil-repellent surfaces that are capable of post-functionalization would have technical implications in surface coatings, membrane separation, and biomedical and analytical technologies.