Inhibition of HIV virus by neutralizing Vhh attached to dual functional liposomes encapsulating dapivirine

Although highly active antiretroviral therapy (HAART) has greatly improved the life expectancy of HIV/AIDS patients, the treatment is not curative. It is a global challenge which fosters an urgent need to develop an effective drug or neutralizing antibody delivery approach for the prevention and treatment of this disease. Due to the low density of envelope spikes with restricted mobility present on the surface of HIV virus, which limit the antibody potency and allow virus mutation and escape from the immune system, it is important for a neutralizing antibody to form bivalent or multivalent bonds with the virus. Liposome constructs could fulfil this need due to the flexible mobility of the membrane with its attached antibodies and the capacity for drug encapsulation. In this study, we evaluated the neutralization activity of a range of liposome formulations in different sizes coated with anti-gp120 llama antibody fragments (Vhhs) conjugated via either non-covalent metal chelation or a covalent linkage. The non-covalent construct demonstrated identical binding affinity to HIV-1 envelope glycoprotein gp120 and neutralizing ability for HIV virus as free Vhh. Although covalently linked Vhh showed significant binding affinity to gp120, it unexpectedly had a lower neutralization potency. This may be due to the comparability in size of the viral and liposome particles restricting the number which can be bound to the liposome surface so involving only a fraction of the antibodies, whereas non-covalently attached antibodies dissociate from the surface after acting with gp120 and free the remainder to bind further viruses. Covalently conjugated Vhh might also trigger the cellular uptake of a liposome-virion complex. To explore the possible ability of the antibody-coated liposomes to have a further function, we encapsulated the hydrophobic antiviral drug dapivirine into both of the non-covalently and covalently conjugated liposome formulations, both of which revealed high efficacy in reducing viral replication in vitro. Thus, dual function liposomes may lead to a novel strategy for the prophylaxis of HIV/AIDS by combining the neutralizing activity of Vhh with antiviral effects of high drug concentrations

Persistence and Titer Changes of Rubella Virus Antibodies in Primiparous Women Who Had Been Vaccinated with Strain RA 27/3 in Junior High School

Taiwan's rubella vaccination program was launched in 1986; each schoolgirl in the third grade of junior high school received one dose of rubella (RA 27/3) vaccine. We reviewed the results of 14,090 prenatal rubella tests for primiparas from three areas of Taiwan during 2002 to 2008 to investigate seronegativity rates and titer changes. In all primiparous women, the average rubella virus seronegativity rate was 6.5% (95% confidence interval [95% CI], 6.1 to 6.9%), and the average rubella virus antibody titer was 65.9 IU/ml (95% CI, 64.7 to 67.1 IU/ml). There were 1,220 women (8.7%) with weakly positive antibody titers (10 to 20 IU/ml). The rubella virus seronegativity rates, which ranged from 5.4 to 9.7%, did not exhibit a linear trend from 9 to 22 years after vaccination (P = 0.201); in contrast, a significant trend appeared in the average rubella virus IgG titer (P = 0.003), dropping from 69.9 IU/ml in the 9th year after vaccination to 54.8 IU/ml in the 22nd year. The mean annual antibody decay rate was −0.77 IU/ml. This study reveals that the level of rubella virus antibodies declined slowly in women of childbearing age who were vaccinated with RA 27/3 at junior high school age. The number of women who were seronegative or had weakly positive antibody titers was still high (15.2%). Therefore, in countries that implement a single-dose regimen in children or teenagers, it should remain an important policy to encourage voluntary immunization in seronegative women and to immunize all postpartum women who are susceptible to rubella virus infection before they leave the hospital