The claim that it is possible to rationally design a structure-based HIV-1 vaccine is based on misconceptions regarding the nature of protein epitopes and of immunological specificity. Attempts to use reverse vaccinology to generate an HIV-1 vaccine on the basis of the structure of viral epitopes bound to monoclonal neutralizing antibodies have failed so far because it was not possible to extrapolate from an observed antigenic structure to the immunogenic structure required in a vaccine. Vaccine immunogenicity depends on numerous extrinsic factors such as the host immunoglobulin gene repertoire, the presence of various cellular and regulatory mechanisms in the immunized host and the process of antibody affinity maturation. All these factors played a role in the appearance of the neutralizing antibody used to select the epitope to be investigated as potential vaccine immunogen, but they cannot be expected to be present in identical form in the host to be vaccinated. It is possible to rationally design and optimize an epitope to fit one particular antibody molecule or to improve the paratope binding efficacy of a monoclonal antibody intended for passive immunotherapy. What is not possible is to rationally design an HIV-1 vaccine immunogen that will elicit a protective polyclonal antibody response of predetermined efficacy. An effective vaccine immunogen can only be discovered by investigating experimentally the immunogenicity of a candidate molecule and demonstrating its ability to induce a protective immune response. It cannot be discovered by determining which epitopes of an engineered antigen molecule are recognized by a neutralizing monoclonal antibody. This means that empirical immunogenicity trials rather than structural analyses of antigens offer the best hope of discovering an HIV-1 vaccine.
Archives of Virology – Springer Journals
Published: Jan 1, 2012
It’s your single place to instantly
discover and read the research
that matters to you.
Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.
All for just $49/month
Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly
Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.
Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.
Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.
All the latest content is available, no embargo periods.
“Hi guys, I cannot tell you how much I love this resource. Incredible. I really believe you've hit the nail on the head with this site in regards to solving the research-purchase issue.”Daniel C.
“Whoa! It’s like Spotify but for academic articles.”@Phil_Robichaud
“I must say, @deepdyve is a fabulous solution to the independent researcher's problem of #access to #information.”@deepthiw
“My last article couldn't be possible without the platform @deepdyve that makes journal papers cheaper.”@JoseServera
Read and print from thousands of top scholarly journals.
Already have an account? Log in
Bookmark this article. You can see your Bookmarks on your DeepDyve Library.
Copy and paste the desired citation format or use the link below to download a file formatted for EndNote
EndNoteExport to EndNote
ok to continue