External and internal HIV-1 antigens have been studied (2,29,46,102,109), each with a variety of antigen modifications. protective immune response in the context of an ongoing infection with an immunodeficiency virus highlights the dire need for a successful prophylactic vaccine that induces a diverse immune response before, not after, a Cenicriviroc Mesylate virus exposure occurs. HIV-1 Vaccine Development HIV-1 vaccine development has continued for decades. Researchers have studied dozens of unique vectors, including vectors from Semliki Forest virus, Venezuelan equine encephalitis virus, adenovirus, adeno-associated virus, modified vaccinia virus Ankara, canarypox/fowlpox, vesicular stomatitis virus, plants, bacteria, and yeast (1,14,43,67,88,98,155,174,175). External and internal HIV-1 antigens have been studied (2,29,46,102,109), each with a variety of antigen modifications. Sequences have encoded consensus, mosaic, and/or scrambled HIV-1 proteins. One concern associated with scrambled sequences is that viral protein three-dimensional structure is lost. When B cell or T cell antigenic epitopes are taken out of context, they may Cenicriviroc Mesylate no longer match those of the virus (26,29,40,56,74,76,91,95,144,154,156,157,159). Several phase III clinical trials have been performed that were not successful (e.g., with two gp120 Env proteins or with an adenovirus 5 vector expressing HIV-1 internal proteins) (36,55,133). One study (RV144) indicated partial protection by a vaccine. This study included 16,000 study participants and used a heterologous prime-boost strategy. The priming vaccine comprised a canarypox vector expressing HIV-1 Env, Gag, and protease proteins, Rabbit polyclonal to ALS2CR3 and the booster vaccine was composed of two purified HIV-1 Env proteins in an alum adjuvant (12,130). In a modified intent-to-treat analysis, data suggested that there were 30% fewer HIV-1 infections in vaccinated individuals compared to controls. Several additional clinical trials are in progress (55). Might scientists design a safe HIV-1 vaccine to match the protection conferred by virus infection? To capture the diverse HIV-1 protein structures that induce protection, researchers study viruses collected longitudinally from infected persons (100,129,132,172). These viruses may be grouped using antibody-antigen Cenicriviroc Mesylate cartography (151) to define proteins with unique antigenic determinants. Then, mutually-exclusive immunotypes may be formulated into vaccine cocktails (21,26,75,76,80,157,179), delivered either as a mixture or in succession. The cocktail vaccine approach has repeatedly yielded successful licensed vaccines in other fields [e.g., rotavirus (34), pneumococcus (16,119), and polio (18C20,82,112)]. In the HIV-1 vaccine field, the cocktail vaccine approach is gaining momentum. Two different goals are fueled. One goal is to induce successive somatic mutations in a B cell clone to generate a rare bNab (74). The second goal is to harness the extraordinary receptor diversity present among mammalian B cells and T cells (11,42,61,71,92), and thereby Cenicriviroc Mesylate recruit an army of diverse lymphocytes to tackle HIV-1 (22,129). Perhaps the cocktail vaccine approach will ultimately advance through clinical trials, satisfy both goals, and prove successful in the HIV-1 field. Parvovirus B19 Infection and Immunity Parvovirus B19 is a small, nonenveloped, single strand DNA virus. The minor capsid protein (VP1) and major capsid protein (VP2) assemble with a ratio of 1 1:20 to form an icosahedron coat. VP1 and VP2 share amino acid sequence at the C-terminus. The VP1?N-terminus contains a unique region (VP1u) that is crucial for virion binding to its target cell (126). Parvovirus B19 is thought to be transmitted primarily through the respiratory route, but the virus can also infect by an Cenicriviroc Mesylate individual’s direct exposure to contaminated blood. The virus specifically infects erythroid progenitor cells by binding globoside (P antigen) and causes transient cessation of erythropoiesis (25,126). Outbreaks of parvovirus infections occur frequently in schools and daycare centers and can cause symptoms in 40% of infected children.