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The inability of a mixture of 4 dengue chimeric viruses to elicit an initial primary neutralizing antibody response in nonhuman primates and susceptible humans was recognized during preclinical testing and explained by the phenomenon of interference (2).
For example, to elicit broadly neutralizing antibodies called VRC01-class antibodies that neutralize 90 percent of known HIV strains, you could try using the HIV envelope protein as your immunogen," Schief said, and added, "But you run into the problem that the envelope protein doesn't bind with any detectable affinity to the B cells needed to launch a broadly neutralizing antibody response.
In this study, the vaccine demonstrated strong neutralizing antibody titers across all three doses tested, exhibiting increasing antibody titers with the escalation of the dose.
We expect that the biological explanations for the development of broadly neutralizing antibody responses," says Poignard, "are likely to be of special relevance to the design of candidate AIDS vaccines and immunization regimens devised to elicit similar antibodies.
Serum samples were obtained from participating pregnant women and their children to measure EV71 neutralizing antibody titers immediately before delivery for pregnant women; at birth for neonates (cord blood); and at 6, 12, 24, 36, and 48 months of age for infants.
Finally, VLPs can induce neutralizing antibody and CTL responses.
When injected into baboons, the two formulations together "exhibited the highest neutralizing antibody response to date," they report.
These new antibodies, which are more potent than other antibodies described to date while maintaining great breadth, attach to a novel, and potentially more accessible site on HIV to facilitate vaccine design," said Dennis Burton, professor of immunology and microbial science and scientific director of the IAVI Neutralizing Antibody Center at The Scripps Research Institute in La Jolla, California.
Funding for the research was provided by the National Institute of Allergy and Infectious Diseases (grants 5R21AI088554, 1UM1AI100663, 1R01AI102766-01A1, P30AI36214); the International AIDS Vaccine Initiative Neutralizing Antibody Consortium; the International AIDS Vaccine Initiative Neutralizing Antibody Center; the March of Dimes; the Bill and Melinda Gates Foundation; The Children's Hospital of Philadelphia; and the Fundacao para a Ciencia e a Tecnologia of Portugal.
The kind of antibody studied is called a broadly cross-reactive neutralizing antibody, and details of its generation could provide a blueprint for effective vaccination, the study's researchers said.
Studies have shown that heterologous neutralizing antibody titers are inversely correlated with severity of a second infection.
This is the work of the Neutralizing Antibody Consortium, a global collaboration of researchers organized by IAVI that will take advances from the Theraclone-IAVI partnership forward.
Having blood samples from such an early stage enabled researchers to pinpoint the particular "founder" virus that triggered the immune system to make an immature broadly neutralizing antibody against HIV, as well as the cell from which that antibody emerged.
4) Subsequently published work by ADARC and collaborators has shown that viremic episodes (due to nonadherence in therapy (5) or a lack of viral suppression while on therapy (6)) were associated with stronger neutralizing antibody responses (5) and HIV-specific CD8 T cell responses (6) among patients treated during acute or early infection, respectively.
Similarly, a separate, recently published report* from the IAVI Neutralizing Antibody Center at The Scripps Research Institute showed how a different broadly neutralizing HIV antibody also binds to the virus via two sugars and a string of amino acid residues.