Titers Of Neutralizing Activity Research Articles

Sustained Responses of Neutralizing Antibodies Against Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in Recovered Patients and Their Therapeutic Applicability.

BackgroundZoonotic coronaviruses have emerged as a global threat by causing fatal respiratory infections. Given the lack of specific antiviral therapies, application of human convalescent plasma retaining neutralizing activity could be a viable therapeutic option that can bridges this gap.MethodsWe traced antibody responses and memory B cells in peripheral blood collected from 70 recovered Middle East respiratory syndrome coronavirus (MERS-CoV) patients for 3 years after the 2015 outbreak in South Korea. We also used a mouse infection model to examine whether the neutralizing activity of collected sera could provide therapeutic benefit in vivo upon lethal MERS-CoV challenge.ResultsAnti-spike-specific IgG responses, including neutralizing activity and antibody-secreting memory B cells, persisted for up to 3 years, especially in MERS patients who suffered from severe pneumonia. Mean antibody titers gradually decreased annually by less than 2-fold. Levels of antibody responses were significantly correlated with fever duration, viral shedding periods, and maximum viral loads observed during infection periods. In a transgenic mice model challenged with lethal doses of MERS-CoV, a significant reduction in viral loads and enhanced survival was observed when therapeutically treated with human plasma retaining a high neutralizing titer (> 1/5000). However, this failed to reduce pulmonary pathogenesis, as revealed by pathological changes in lungs and initial weight loss.ConclusionsHigh titers of neutralizing activity are required for suppressive effect on the viral replication but may not be sufficient to reduce inflammatory lesions upon fatal infection. Therefore, immune sera with high neutralizing activity must be carefully selected for plasma therapy of zoonotic coronavirus infection.

Immunopotentiation of Staphylococcus aureus type 5 capsular polysaccharide co-entrapped in liposomes with α-toxin

Immunopotentiation of Staphylococcus aureus type 5 capsular polysaccharide (CP5) by use of liposomes as an alternative to protein–polysaccharide conjugates was investigated. Mice were immunized twice with cationic liposomes containing CP5 alone or CP5 co-entrapped with α-toxin or heat-detoxified α-toxin. Immunogenicity of these different antigens was compared with CP5–α-toxin conjugates. Antibodies against CP5 were elicited in mice immunized with conjugates or liposomes containing co-entrapped CP5 and α-toxin. Liposomes containing CP5 alone or co-entrapped CP5 and α-toxoid failed to induce antibodies against CP5. All the preparations entailed an antibody response against α-toxin and highest antibody and neutralizing activity titers were obtained with liposomes. These results show that liposomes can be used to immunopotentiate CP5, however, a co-incorporated protein able to insert lipids bilayers is probably required.

Phylogenetic and serological characterization of two Ugandan HIV-1 isolates.

HIV-1 isolates Ug06 and Ug23 were established in culture from peripheral blood mononuclear cells (PBMCs) of Ugandan subjects. The isolates were studied for phylogenetic and serological relationships with each other and with the laboratory strains, HTLV-IIIB and HIV-1MN. The results suggest that the Ugandan isolates are related to different subgroups of African viruses with 17.3% of genetic distance between UG06 and the U455 provirus (Uganda); and 12.6% of genetic distance between UG23 and the JY1 provirus (Zaire). Analysis of the predicted amino acid sequences for Ug06 and Ug23 showed marked sequence heterogeneity in the V3 region and CD4-binding site. A conserved amino acid sequence was identified in the C-terminal immunodominant region of the envelope glycoprotein gp120. The isolates were compared in virus-neutralization experiments with HTLV-IIIB and HIV-1MN stocks, using panels of Western blot-positive North American and Ugandan sera. The North American serum samples showed broad neutralizing activity against both of the Ugandan isolates. However, the Ugandan serum panel demonstrated strain-specific activity against either Ug06 or Ug23. Furthermore, the African serum specimens showed higher prevalence and titers of neutralizing activity against the HIV-1MN stock as compared with HTLV-IIIB.

Antigenic characterization of poliovirus type 3 using monoclonal antibodies.

Hybridoma cell lines secreting monoclonal antibodies to type 3 poliovirus were prepared, and their reactivity with infectious virus (D antigen), empty particles (C antigen), and isolated virion capsid proteins ( VPs ) were examined. Eight antibodies reacted with epitopes common to D and C antigens, and all of these possessed high titers of neutralizing activity. However, only 12 of 19 antibodies that reacted exclusively with D antigen neutralized virus infectivity, and some of these reacted only with strains of virus with T1-oligonucleotide maps identical or similar to that of Sabin vaccine polio virus. These antibodies will be of value in identifying strains of virus derived from Sabin vaccine. None of the 20 monoclonal antibodies that neutralized type 3 poliovirus strains reacted in immunoblot experiments with isolated virion capsid proteins. However, six of the 24 antibodies that reacted only with noninfectious C antigen bound to VP1 and VP3, and three of these antibodies also reacted with proteins of poliovirus types 1 or 2. The lack of reactivity of neutralizing monoclonal antibodies with isolated viral proteins suggests that the antigenic properties of proteins are determined by their arrangement in the virus and not simply by amino acid sequence.

Infectious mononucleosis: appearance of neutralizing antibody to Epstein-Barr virus measured by inhibition of formation of lymphoblastoid cell lines.

Sera taken before illness and during convalescence from patients with infectious mononucleosis (IM) were examined for their ability to neutralize the capacity of Epstein-Barr virus (EBV) to stimulate formation of lymphoblastoid cell lines from human leukocytes in vitro. Neutralizing activity was not detected in 13 of 15 sera taken before illness and was present at a dilution of 1:4 or higher in all of 24 sera taken after illness. EBV-neutralizing activity was found in sera collected during the first week of illness and was also demonstrated in a serum obtained many years after illness. The titer of neutralizing activity in sera of two patients studied sequentially did not change significantly during the first year after IM. The results demonstrate appearance of EBV-neutralizing antibody in IM and support previous seroepidemiologic studies which indicate that EBV is the etiologic agent of IM.