Safety and Immunogenicity of a Replication-Defective Adenovirus Type 5 HIV Vaccine in Ad5-Seronegative Persons: A Randomized Clinical Trial (HVTN 054)

BACKGROUND: Individuals without prior immunity to a vaccine vector may be more sensitive to reactions following injection, but may also show optimal immune responses to vaccine antigens. To assess safety and maximal tolerated dose of an adenoviral vaccine vector in volunteers without prior immunity, we evaluated a recombinant replication-defective adenovirus type 5 (rAd5) vaccine expressing HIV-1 Gag, Pol, and multiclade Env proteins, VRC-HIVADV014-00-VP, in a randomized, double-blind, dose-escalation, multicenter trial (HVTN study 054) in HIV-1-seronegative participants without detectable neutralizing antibodies (nAb) to the vector. As secondary outcomes, we also assessed T-cell and antibody responses. METHODOLOGY/PRINCIPAL FINDINGS: Volunteers received one dose of vaccine at either 10(10) or 10(11) adenovector particle units, or placebo. T-cell responses were measured against pools of global potential T-cell epitope peptides. HIV-1 binding and neutralizing antibodies were assessed. Systemic reactogenicity was greater at the higher dose, but the vaccine was well tolerated at both doses. Although no HIV infections occurred, commercial diagnostic assays were positive in 87% of vaccinees one year after vaccination. More than 85% of vaccinees developed HIV-1-specific T-cell responses detected by IFN-γ ELISpot and ICS assays at day 28. T-cell responses were: CD8-biased; evenly distributed across the three HIV-1 antigens; not substantially increased at the higher dose; and detected at similar frequencies one year following injection. The vaccine induced binding antibodies against at least one HIV-1 Env antigen in all recipients. CONCLUSIONS/SIGNIFICANCE: This vaccine appeared safe and was highly immunogenic following a single dose in human volunteers without prior nAb against the vector. TRIAL REGISTRATION: ClinicalTrials.gov NCT00119873

Cross-Border Mobility of Self-Initiated and Organizational Expatriates

Globalization in the late twentieth and early twenty-first centuries has been marked by an increase in cross-border mobility of the highly skilled. Though self-initiated expatriation is a widespread phenomenon, it has received relatively little attention in the academic literature. Furthermore, large-scale studies that track self-initiated and organizational expatriates together, over time and across geographies, are noticeably absent from the literature. Consequently, our understanding of these two forms of mobility is relatively limited. This study, which is the first large-scale analysis of the trends in and patterns of the mobility of organization-initiated expatriates and self-initiated expatriates, attempts to fill this gap by analyzing the mobility patterns of 55,915 highly skilled individuals who made 76,660 cross-border moves between 1990 and 2006. Specifically, we analyze patterns of geographic mobility and then examine the rate, duration, and direction of self-initiated and organizational expatriation over time. Finally, we consider demographic differences in mobility between the two groups

Determinants of transnational social capital: opportunity–investment–ability perspective

This study suggests that it is critical for executives todeveloptransnational social capital(TSC), or professionalrelationships and ties that span national borders. We firstprovide a conceptual framework and careful operationaliza-tion of TSC that differentiates between bonding and bridg-ing forms of social capital. We then examine the effect ofthree key determinants—opportunity, investment and abil-ity—on the TSC of executives. Using detailed survey dataon 227 executives, our analysis suggests that internationalexperience, investment in communicating with cross-borderties and cosmopolitan ability have direct effects on overallTSC. We further demonstrate that international experienceand cosmopolitan ability affect both bridging and bonding,but that investment in cross-border communication onlyaffects bridging social capital. The study proposes thatsocial capital is becoming more and more transnational asconnections, interactions and transactions increasingly spannational borders, which has implications for internationalbusiness and human resource management. Given our find-ings, it would make sense for global organizations to paymore attention to these, if they would like their membersto develop this resource. We point out benefits to organiza-tions and individuals

Careers of highly educated self-initiated expatriates : observations from studies among Finnish business professionals

This chapter reviews existing literature about the careers of self-initiated expatriates and analyzes the different studies carried out among university level educated Finnish business professionals. A series of studies carried out among members of the Finnish Association of Business School Graduates during the last 15 years was cross-analyzed. The studies are based on three surveys and further interviews among their expatriate members (1999, 2004 and a follow-up study in 2012) also involving SIEs. Therefore, this chapter provide an overview of what we know about the careers of Finnish SIEs and show evidence of (1) their career motives, (2) the role of family considerations in the career decision making of SIEs, (3) the development of career capital and social capital during SIE-experiences, and also (4) longer-term career impacts of SIE-experiences. Based on the literature review and analysis of above mentioned studies we highlight the gaps in in the knowledge about SIEs and suggest areas where further research is needed.fi=vertaisarvioitu|en=peerReviewed

Clinical Assessment of a Recombinant Simian Adenovirus ChAd63: A Potent New Vaccine Vector

Background. Vaccine development in human Plasmodium falciparum malaria has been hampered by the exceptionally high levels of CD8+ T cells required for efficacy. Use of potently immunogenic human adenoviruses as vaccine vectors could overcome this problem, but these are limited by preexisting immunity to human adenoviruses

Synergism/complementarity of recombinant adenoviral vectors and other vaccination platforms during induction of protective immunity against malaria

The lack of immunogenicity of most malaria antigens and the complex immune responses required for achieving protective immunity against this infectious disease have traditionally hampered the development of an efficient human malaria vaccine. The current boom in development of recombinant viral vectors and their use in prime-boost protocols that result in enhanced immune outcomes have increased the number of malaria vaccine candidates that access pre-clinical and clinical trials. In the frontline, adenoviruses and poxviruses seem to be giving the best immunization results in experimental animals and their mutual combination, or their combination with recombinant proteins (formulated in adjuvants and given in sequence or being given as protein/virus admixtures), has been shown to reach unprecedented levels of anti-malaria immunity that predictably will be somehow reproduced in the human setting. However, all this optimism was previously seen in the malaria vaccine development field without many real applicable results to date. We describe here the current state-of-the-art in the field of recombinant adenovirus research for malaria vaccine development, in particular referring to their use in combination with other immunogens in heterologous prime-boost protocols, while trying to simultaneously show our contributions and point of view on this subject

Safety and Immunogenicity of an HIV Adenoviral Vector Boost after DNA Plasmid Vaccine Prime by Route of Administration: A Randomized Clinical Trial

In the development of HIV vaccines, improving immunogenicity while maintaining safety is critical. Route of administration can be an important factor.This multicenter, open-label, randomized trial, HVTN 069, compared routes of administration on safety and immunogenicity of a DNA vaccine prime given intramuscularly at 0, 1 and 2 months and a recombinant replication-defective adenovirus type 5 (rAd5) vaccine boost given at 6 months by intramuscular (IM), intradermal (ID), or subcutaneous (SC) route. Randomization was computer-generated by a central data management center; participants and staff were not blinded to group assignment. The outcomes were vaccine reactogenicity and humoral and cellular immunogenicity. Ninety healthy, HIV-1 uninfected adults in the US and Peru, aged 18-50 were enrolled and randomized. Due to the results of the Step Study, injections with rAd5 vaccine were halted; thus 61 received the booster dose of rAd5 vaccine (IM: 20; ID:21; SC:20). After the rAd5 boost, significant differences by study arm were found in severity of headache, pain and erythema/induration. Immune responses (binding and neutralizing antibodies, IFN-γ ELISpot HIV-specific responses and CD4+ and CD8+ T-cell responses by ICS) at four weeks after the rAd5 booster were not significantly different by administration route of the rAd5 vaccine boost (Binding antibody responses: IM: 66.7%; ID: 70.0%; SC: 77.8%; neutralizing antibody responses: IM: 11.1%; ID: 0.0%; SC 16.7%; ELISpot responses: IM: 46.7%; ID: 35.3%; SC: 44.4%; CD4+ T-cell responses: IM: 29.4%; ID: 20.0%; SC: 35.3%; CD8+ T-cell responses: IM: 29.4%; ID: 16.7%; SC: 50.0%.)This study was limited by the reduced sample size. The higher frequency of local reactions after ID and SC administration and the lack of sufficient evidence to show that there were any differences in immunogenicity by route of administration do not support changing route of administration for the rAd5 boost.ClinicalTrials.gov NCT00384787

Transcultural Brokerage: The Role of Cosmopolitans in Bridging Structural and Cultural Holes

The growth and proliferation of global systems and transnational cultures have generated larger and more diverse types of cosmopolitans, all of whom span conventional social boundaries. Understanding this diversity is increasingly important because cosmopolitans often bridge across a wide range of transnational and global networks within and across global organizations. Drawing on multiple disciplines, we conceptualize cosmopolitanism as an embodied disposition characterized by high levels of cultural transcendence and openness that are manifested in and enacted along varied trajectories of cultural embeddedness in one’s own culture and cultural engagement with the cultural Other. We then propose an analytical framework for the influence of cosmopolitan disposition on transcultural brokerage processes, specifically on bridging structural and cultural holes. Finally, we present a typology of cosmopolitan brokers and their corresponding practices and activities as they engage in transcultural brokerage. By recognizing the diversity of cosmopolitans and their respective dispositions, we significantly expand the pool of “global talent” beyond the traditional focus on expatriates, and we challenge the conventional wisdom on who counts as talent in an interconnected world