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The enduring pandemic threat of Avian influenza A/H5N1 was underscored in January 2014 when the first North American H5N1 death was documented in a Canadian who returned from China [1, 2]. For almost 2 decades preceding this fatality, the pandemic potential of avian H5N1 influenza has been of concern [3, 4]. More than 30 sporadic cases of H5N1 infection occurred in 2013, for a total of 648 laboratory-confirmed illnesses, and ∼60% mortality was reported to the World Health Organization by 16 countries from 2003 to 2013 [5]. The repeated outbreaks of novel and variant avian and swine influenza viruses in humans have led to efforts to produce vaccines against these pandemic or potential pandemic viruses. Clinical trials of candidate H5N1 vaccines revealed that these hemagglutinins (HAs) were poor vaccine antigens [6–8], but antibody responses could be improved substantially with adjuvants [9]. Because vaccine supplies may be limited, it is also important to lower the antigen dose required to induce protection in order to make limited vaccine supplies available for protection of more people. For stockpiled vaccine antigens that require an adjuvant to achieve protective antibody titers, 1 rapid response approach would be to match the relevant antigen to a stockpiled adjuvant at pandemic onset and mix the reagents at designated field sites—the mix-and-match approach tested here. The squalene-containing oil-in-water emulsion adjuvant, MF59, improved the antibody response, permitted dose sparing, and enhanced efficacy [10] when paired with inactivated influenza vaccines [11–14]. MF59-adjuvanted seasonal influenza vaccines were first licensed for the elderly [15] by the European Union in 1997 and—along with MF59-adjuvanted 2009 H1N1 pandemic vaccines—have subsequently been licensed in more than 30 countries with an excellent safety profile and over 65 million doses delivered [16]. MF59-adjuvanted vaccines have not been licensed in the United States. However, the US Department of Health and Human Services (HHS) Biomedical Advanced Research and Development Authority (BARDA) has procured in the National Pre-pandemic Influenza Vaccine Stockpile both H5N1 vaccines and the oil-in-water adjuvants MF59 and AS03. Here, we studied a mix-and-match tactic that paired a stockpiled H5N1 antigen from one manufacturer with stockpiled MF59 adjuvant from another manufacturer, and we demonstrated the potential of point-of-use mixing as a flexile logistical tactic for rapid deployment of stockpiled vaccine reagents should an H5N1 pandemic occur.

Background Vitamin D deficiency is common in HIV-infected individuals. In adults, traditional and HIV-related factors play a role in vitamin D status, and deficiency appears to impair immune restoration and exacerbate HIV complications, like cardiovascular disease (CVD). This study sought to determine factors contributing to vitamin D status in HIV-infected youth and investigate the relationship with CVD risk, inflammation and immune restoration. Methods HIV-infected subjects (1-25 years old) were enrolled prospectively along with healthy controls that were group-matched by age, sex and race. HIV data were collected for the HIV-infected group, while traditional risk factors, including vitamin D intake, sun exposure, skin pigmentation, physical activity level and body mass index (BMI) were collected for both groups. Fasting lipids, plasma 25-hydroxyvitamin D (25[OH]D), and inflammation markers were measured. Results In total, 200 HIV-infected subjects and 50 controls were enrolled. HIV group had 53% male, 95% Black and a mean age of 17.2 ±4.6 years. There was no difference in 25(OH)D between groups; 77% of HIV+ and 74% of controls had 25(OH)DConclusions Vitamin D deficiency is common among HIV-infected youth. However, HIV factors, CVD risk, inflammation and immune restoration do not appear to have the same relationship with vitamin D as has been shown in adults. Supplementation trials are needed to determine if increasing 25(OH)D concentrations could better elucidate these relationships.