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The development of a sterilizing vaccine against malaria remains one of the highest priorities for global health research. While sporozoite vaccines targeting the pre-erythrocytic stage show great promise, it has not been possible to maintain efficacy long-term, likely due to an inability of these vaccines to maintain effector memory T cell responses in the liver. Vaccines based on human cytomegalovirus (HCMV) might overcome this limitation since vectors based on rhesus CMV (RhCMV), the homologous virus in rhesus macaques (RM), elicit and indefinitely maintain high frequency, non-exhausted effector memory T cells in extralymphoid tissues, including the liver. Moreover, RhCMV strain 68-1 elicits CD8+ T cells broadly recognizing unconventional epitopes exclusively restricted by MHC-II and MHC-E. To evaluate the potential of these unique immune responses to protect against malaria, we expressed four Plasmodium knowlesi (Pk) antigens (CSP, AMA1, SSP2/TRAP, MSP1c) in RhCMV 68-1 or in Rh189-deleted 68-1, which additionally elicits canonical MHC-Ia-restricted CD8+ T cells. Upon inoculation of RM with either of these Pk Ag expressing RhCMV vaccines, we obtained T cell responses to each of the four Pk antigens. Upon challenge with Pk sporozoites we observed a delayed appearance of blood stage parasites in vaccinated RM consistent with a 75-80% reduction of parasite release from the liver. Moreover, the Rh189-deleted RhCMV/Pk vectors elicited sterile protection in one RM. Once in the blood, parasite growth was not affected. In contrast to T cell responses induced by Pk infection, RhCMV vectors maintained sustained T cell responses to all four malaria antigens in the liver post-challenge. The delayed appearance of blood stage parasites is thus likely due to a T cell-mediated inhibition of liver stage parasite development. As such, this vaccine approach can be used to efficiently test new T cell antigens, improve current vaccines targeting the liver stage and complement vaccines targeting erythrocytic antigens.

Complete vaccine-mediated immune control of highly pathogenic Mycobacterium tuberculosis is possible if immune effector responses can intercept the infection at its earliest stages. Despite widespread use of the bacille Calmette–Guérin (BCG) vaccine, tuberculosis (TB) remains a leading cause of global mortality from a single infectious agent ( Mycobacterium tuberculosis or Mtb). Here, over two independent Mtb challenge studies, we demonstrate that subcutaneous vaccination of rhesus macaques (RMs) with rhesus cytomegalovirus vectors encoding Mtb antigen inserts (hereafter referred to as RhCMV/TB)—which elicit and maintain highly effector-differentiated, circulating and tissue-resident Mtb-specific CD4 + and CD8 + memory T cell responses—can reduce the overall (pulmonary and extrapulmonary) extent of Mtb infection and disease by 68%, as compared to that in unvaccinated controls, after intrabronchial challenge with the Erdman strain of Mtb at ∼1 year after the first vaccination. Fourteen of 34 RhCMV/TB-vaccinated RMs (41%) across both studies showed no TB disease by computed tomography scans or at necropsy after challenge (as compared to 0 of 17 unvaccinated controls), and ten of these RMs were Mtb-culture-negative for all tissues, an exceptional long-term vaccine effect in the RM challenge model with the Erdman strain of Mtb. These results suggest that complete vaccine-mediated immune control of highly pathogenic Mtb is possible if immune effector responses can intercept Mtb infection at its earliest stages.

Cellular immune responses in rhesus macaques ( Macaca mulatta ) vaccinated with cytomegalovirus vectors expressing SIV proteins are able to stringently control highly pathogenic SIV infection, regardless of the route of challenge, after systemic spread; immunological and virological analyses of protected macaques followed for up to 3 years suggest that persistent immune surveillance by vaccine-elicited immune responses may have cleared the infection. Vaccine combats virulent SIV infection Work on potential vaccines against human immunodeficiency viruses (HIV) and the simian equivalent (SIV) has so far proved largely fruitless. This study makes some progress by exploiting the recent observation that the pathogens appear vulnerable to immune control or pharmacological clearance in the first few hours to days of infection. Rhesus macaques vaccinated with SIV protein-expressing rhesus cytomegalovirus (RhCMV/SIV) vectors developed durable resistance to the highly pathogenic SIVmac239 after challenge by vaginal and intravenous routes. Some of the vaccinated animals have controlled viral replication for 1 to 3 years with no demonstrable evidence for residual virus, raising the possibility that the vaccine- elicited immune responses may in fact have cleared the initial infection. Established infections with the human and simian immunodeficiency viruses (HIV and SIV, respectively) are thought to be permanent with even the most effective immune responses and antiretroviral therapies only able to control, but not clear, these infections 1 , 2 , 3 , 4 . Whether the residual virus that maintains these infections is vulnerable to clearance is a question of central importance to the future management of millions of HIV-infected individuals. We recently reported that approximately 50% of rhesus macaques (RM; Macaca mulatta ) vaccinated with SIV protein-expressing rhesus cytomegalovirus (RhCMV/SIV) vectors manifest durable, aviraemic control of infection with the highly pathogenic strain SIVmac239 (ref. 5 ). Here we show that regardless of the route of challenge, RhCMV/SIV vector-elicited immune responses control SIVmac239 after demonstrable lymphatic and haematogenous viral dissemination, and that replication-competent SIV persists in several sites for weeks to months. Over time, however, protected RM lost signs of SIV infection, showing a consistent lack of measurable plasma- or tissue-associated virus using ultrasensitive assays, and a loss of T-cell reactivity to SIV determinants not in the vaccine. Extensive ultrasensitive quantitative PCR and quantitative PCR with reverse transcription analyses of tissues from RhCMV/SIV vector-protected RM necropsied 69–172 weeks after challenge did not detect SIV RNA or DNA sequences above background levels, and replication-competent SIV was not detected in these RM by extensive co-culture analysis of tissues or by adoptive transfer of 60 million haematolymphoid cells to naive RM. These data provide compelling evidence for progressive clearance of a pathogenic lentiviral infection, and suggest that some lentiviral reservoirs may be susceptible to the continuous effector memory T-cell-mediated immune surveillance elicited and maintained by cytomegalovirus vectors.

One vaccine strategy being pursued against HIV is to generate protection that is dependent on cell-mediated, rather than humoral, immune responses. A cytomegalovirus (CMV)–vectored vaccine that expresses simian immunodeficiency virus (SIV) antigens exhibits stringent and durable viral control upon SIV challenge in approximately half of vaccinated rhesus macaques. Hansen et al. ( 10.1126/science.1237874 , see the Perspective by Goonetilleke and McMichael ) sought to determine the basis for the protection and discovered that the CD8 + T cell response in vaccinated monkeys does not target canonical SIV epitopes, which SIV is known to escape, but rather generates a broad, promiscuous response. A vaccine that uses one virus to deliver components of a second virus elicits T cells that recognize noncanonical epitopes. [Also see Perspective by Goonetilleke and McMichael ] CD8 + T cell responses focus on a small fraction of pathogen- or vaccine-encoded peptides, and for some pathogens, these restricted recognition hierarchies limit the effectiveness of antipathogen immunity. We found that simian immunodeficiency virus (SIV) protein–expressing rhesus cytomegalovirus (RhCMV) vectors elicit SIV-specific CD8 + T cells that recognize unusual, diverse, and highly promiscuous epitopes, including dominant responses to epitopes restricted by class II major histocompatibility complex (MHC) molecules. Induction of canonical SIV epitope–specific CD8 + T cell responses is suppressed by the RhCMV-encoded Rh189 gene (corresponding to human CMV US11 ), and the promiscuous MHC class I– and class II–restricted CD8 + T cell responses occur only in the absence of the Rh157.5 , Rh157.4 , and Rh157.6 (human CMV UL128 , UL130 , and UL131 ) genes. Thus, CMV vectors can be genetically programmed to achieve distinct patterns of CD8 + T cell epitope recognition.

This historical Case report has been prepared to remember and recognize the excellent work carried out by a few pioneers of the \"science of fingerprints\" in New Zealand and our specialist role as latent print examiners. The trial for Dennis Gunn, accused of murdering Mr. Augustus Briathwaite, the Ponsonby postmaster, in many ways is similar to a Daubert hearing, except that it occurred in 1920 in New Zealand, nearly 100 years ago. This report summarizes key elements of the fingerprint evidence and the resulting murder trial that led to the conviction and subsequent execution of Dennis Gunn. The trial considered issues such as the permanence and uniqueness of fingerprints, reliability of the evidence, forgery, proficiency testing, peer review, and the minimum number of points needed to individualize. At the conclusion of the trial, the Minister of Justice ensured that an authentic report of the trial was printed so that the e~ deuce was available to the general public.

This corrects the article DOI: 10.1038/nature12519.

Conventional law enforcement doctrine and wisdom, as propagated by the Federal Bureau of Investigation, the news media, Hollywood movies, TV shows, and academic research, state that the traditional profile of a serial killer universally focuses on finding a White male perpetrator. However, limited research into the pathology and activities of Black serial killers such as Samuel Little suggests that this conventional law enforcement wisdom and doctrine is both false as a narrative and investigative premise. Additional research is needed to explore such recent findings or identify them as possible “outlier,” This study focuses upon (a) the repercussions of institutional acceptance of the incorrect stereotype that serial killers are predominately White males; (b) that Black serial killers are under-estimated in American society; and (c) that there is a need for further scholarly research focused on Black serial killers to protect their potential victims and to develop more effective investigative methodologies to detect, investigate, and apprehend them for criminal prosecution. This study employs as research methodologies both Case Studies and Critical Discourse Analysis to illustrate topologies that distinguish between Black and White serial killers as well as their impact upon American society and potential victims. This topic is also essential to the public, news and entertainment media, academic research, and law enforcement agencies.

Gauging quantity and quality of detail in a fingerprint is a central part of the identification process. It is imperative that an examiner be aware of and be able to identify all features of a mark to assist in an identification. Although pores have often been sidelined as being unreliably reproduced, they can be a useful tool to assist in comparative ridgeology. This case study is an excellent example of how useful pores can be when there are insufficient traditional points of comparison to individualize. [PUBLICATION ABSTRACT]

Nature 502, 100–104 (2013); doi:10.1038/nature12519 The Acknowledgements section of this Letter should have included the following sentence: “We acknowledge the contribution of M. A. Jarvis to the design, construction and initial in vitro characterization of all the strain 68.1-derived RhCMV vectorsused in this study, including both previously published RhCMV/SIV vectors and a previously unpublished vector expressing an Mycobacterium tuberculosis Ag85B–ESAT6 fusion protein, used as a negative control in this study.