Human Cytomegalovirus (HCMV) utilizes two different pathways for host cell entry. HCMV entry into fibroblasts requires glycoproteins gB and gH/gL, whereas HCMV entry into epithelial and endothelial cells (EC) requires an additional complex composed of gH, gL, UL128, UL130, and UL131A, referred to as the gH/gL-pentamer complex (gH/gL-PC). While there are no established correlates of protection against HCMV, antibodies are thought to be important in controlling infection. Neutralizing antibodies (NAb) that prevent gH/gL-PC mediated entry into EC are candidates to be assessed for in vivo protective function. However, these potent NAb are predominantly directed against conformational epitopes derived from the assembled gH/gL-PC. To address these concerns, we constructed Modified Vaccinia Ankara (MVA) viruses co-expressing all five gH/gL-PC subunits (MVA-gH/gL-PC), subsets of gH/gL-PC subunits (gH/gL or UL128/UL130/UL131A), or the gB subunit from HCMV strain TB40/E. We provide evidence for cell surface expression and assembly of complexes expressing full-length gH or gB, or their secretion when the corresponding transmembrane domains are deleted. Mice or rhesus macaques (RM) were vaccinated three times with MVA recombinants and serum NAb titers that prevented 50% infection of human EC or fibroblasts by HCMV TB40/E were determined. NAb responses induced by MVA-gH/gL-PC blocked HCMV infection of EC with potencies that were two orders of magnitude greater than those induced by MVA expressing gH/gL, UL128-UL131A, or gB. In addition, MVA-gH/gL-PC induced NAb responses that were durable and efficacious to prevent HCMV infection of Hofbauer macrophages, a fetal-derived cell localized within the placenta. NAb were also detectable in saliva of vaccinated RM and reached serum peak levels comparable to NAb titers found in HCMV hyperimmune globulins. This vaccine based on a translational poxvirus platform co-delivers all five HCMV gH/gL-PC subunits to achieve robust humoral responses that neutralize HCMV infection of EC, placental macrophages and fibroblasts, properties of potential value in a prophylactic vaccine.

BackgroundUp to half of all new HIV cases in Los Angeles may be caused by the 20-30% of men who have sex with men (MSM) with unrecognized HIV infection. Racial/ethnic minority MSM are at particularly high risk for being sero-unaware and due to stigma and poor healthcare access might benefit from novel private, self-testing methods, such as the recently FDA-approved OraQuick® In-Home HIV Test.MethodsFrom July-November 2013, we undertook a pilot study to examine the feasibility of a voucher program for free OraQuick® tests targeting African American MSM in Los Angeles. We determined feasibility based on: (1) the establishment of a voucher redemption and third-party payment system, (2) the willingness of community-based organizations (CBOs) to disseminate vouchers, and (3) the collection of user demographics, test and linkage-to-care results with an anonymous telephone survey.ResultsWe partnered with Walgreens® to create a voucher and third-party reimbursement system for free OraQuick® tests. Voucher distribution was divided into two periods. In total, 641 vouchers were supplied to CBOs: 274 (42.7%) went to clients and of those 53 (19.3%) were redeemed. Fifty (18.2%) of the 274 clients were surveyed: 44 (88%) were African American, 39 (78%) reported being likely to repeat voucher use, 44 (88%) reported reviewing pre-test information, and 37 (74%) the post-test information. Three (6%) of 50 survey respondents reported newly testing HIV-positive of whom all (100%) reported seeking medical care. Two withheld their results, both of whom also sought medical care.ConclusionsDeveloping and partnering with a commercial pharmacy to institute a voucher system to facilitate HIV self-testing with linkage-to-care was feasible. Our findings suggest the voucher program was associated with increasing the identification of new cases of HIV infection with high rates of linkage to care. Expanded research and evaluation of voucher programs for HIV self-test kits among high-risk groups is warranted.

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