AIMS Public Health , 2015, 2(2): 183-193. doi: 10.3934/publichealth.2015.2.183.

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Why Does the Molecular Structure of Broadly Neutralizing Monoclonal Antibodies Isolated from Individuals Infected with HIV-1 not Inform the Rational Design of an HIV-1 Vaccine?

Marc H V Van Regenmortel

CNRS, UMR7242 - Institut de Recherche de l'Ecole de Biotechnologie de Strasbourg (IREBS), Université de Strasbourg, Illkirch 67400, France

Received date: , Accepted date: , Published date:

Special Issues: Overcoming the barriers that impede HIV vaccine development and testing

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It is commonly assumed that neutralizing Mabs that bind to the HIV-1 Env glycoprotein are more specific reagents than anti-HIV-1 polyclonal antisera and that knowledge of the structure of these Mabs facilitates the rational design of effective HIV-1 vaccine immunogens. However, after more than ten years of unsuccessful experimentation using the structure-based reverse vaccinology approach, it is now evident that it is not possible to infer from the structure of neutralizing Mabs which HIV immunogens induced their formation nor which vaccine immunogens will elicit similar Abs in an immunized host. The use of Mabs for developing an HIV-1 vaccine was counterproductive because it overlooked the fact that the apparent specificity of a Mab very much depends on the selection procedure used to obtain it and also did not take into account that an antibody is never monospecific for a single epitope but is always polyspecific for many epitopes. When the rationale of the proponents of the unsuccessful rational design strategy is analyzed, it appears that investigators who claim they are designing a vaccine immunogen are only improving the binding reactivity of a single epitope-paratope pair and are not actually designing an immunogen able to generate protective antibodies. The task of a designer consists in imagining what type of immunogen is likely to elicit a protective immune response but in the absence of knowledge regarding which features of the immune system are responsible for producing a functional neutralizing activity in antibodies, it is not feasible to intentionally optimize a potential immunogen candidate in order to obtain the desired outcome. The only available option is actually to test possible solutions by trial-and-error experiments until the preset goal is perhaps attained. Rational design and empirical approaches in HIV vaccine research should thus not be opposed as alternative options since empirical testing is an integral part of a so-called design strategy.
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Keywords:  antibody polyspecificity; Darwinian natural selection; design metaphor; discontinuous HIV epitopes; rational HIV-1 vaccine design; reverse vaccinology

Citation: Marc H V Van Regenmortel. Why Does the Molecular Structure of Broadly Neutralizing Monoclonal Antibodies Isolated from Individuals Infected with HIV-1 not Inform the Rational Design of an HIV-1 Vaccine?. AIMS Public Health , 2015, 2(2): 183-193. doi: 10.3934/publichealth.2015.2.183

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This article has been cited by: 

  • 1. M.H.V. van Regenmortel, The metaphor that viruses are living is alive and well, but it is no more than a metaphor, Studies in History and Philosophy of Science Part C: Studies in History and Philosophy of Biological and Biomedical Sciences, 2016, 10.1016/j.shpsc.2016.02.017
  • 2. Marc H. V. Van Regenmortel, Commentary: Basic Research in HIV Vaccinology Is Hampered by Reductionist Thinking, Frontiers in Immunology, 2016, 7, 10.3389/fimmu.2016.00266
  • 3. Marc Van Regenmortel, Structure-Based Reverse Vaccinology Failed in the Case of HIV Because it Disregarded Accepted Immunological Theory, International Journal of Molecular Sciences, 2016, 17, 9, 1591, 10.3390/ijms17091591
  • 4. Krishna Sundari Sattiraju, Srishti Kotiyal, Asmita Arora, Mahima Maheshwari, , Environmental Biotechnology: For Sustainable Future, 2019, Chapter 8, 199, 10.1007/978-981-10-7284-0_8
  • 5. Marc H V Van Regenmortel, , HIV/AIDS: Immunochemistry, Reductionism and Vaccine Design, 2019, Chapter 21, 249, 10.1007/978-3-030-32459-9_21
  • 6. Marc H V Van Regenmortel, , HIV/AIDS: Immunochemistry, Reductionism and Vaccine Design, 2019, Chapter 10, 127, 10.1007/978-3-030-32459-9_10
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  • 8. Marc H V Van Regenmortel, , HIV/AIDS: Immunochemistry, Reductionism and Vaccine Design, 2019, Chapter 11, 131, 10.1007/978-3-030-32459-9_11

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Copyright Info: 2015, Marc H V Van Regenmortel, licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution Licese (http://creativecommons.org/licenses/by/4.0)

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