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Girard M.P.,French National Academy of Medicine | Le-Grand R.,University Paris - Sud | Picot V.,Fondation Merieux | Longuet C.,Fondation Merieux | Nabel G.J.,Sanofi S.A.
Vaccine | Year: 2016

The 2015 Cent Gardes Conference on HIV vaccines took place on October 25-27 at the Merieux Foundation Conference Center in Veyrier du Lac, near Annecy, France. The meeting reviewed progress in the development of HIV vaccines and identified new directions of future research. The field has advanced incrementally over the past year but major progress will require additional information from new clinical trials. In this article, we review the presentations on humoral immune responses to HIV, and highlight the difficulty of eliciting broadly neutralizing antibodies by vaccination. Advances in cellular immunity for HIV prevention will be reviewed separately, in a following article. © 2016. Source

Girard M.P.,French National Academy of Medicine | Picot V.,Fondation Merieux | Longuet C.,Fondation Merieux | Nabel G.J.,Sanofi S.A.
Vaccine | Year: 2013

The Cent Gardes Conference on HIV Vaccines took place on November 5-7, 2012 at the Fondation Mérieux Conference Center, Annecy, France. The aim of the meeting was to review the B cell response to human immunodeficiency virus-1 (HIV-1) infection and immunization, from broadly neutralizing antibodies (bnAbs) to non-neutralizing antibodies (n-nAbs). The production of cross-reactive bnAbs is one of the greatest challenges in HIV-1 vaccine development. In natural HIV infection, bnAbs are observed in only a minority of infected individuals and take a few years to develop. This report presents a comprehensive review of how these Abs arise, the possible role of viral evolution, and the activation and maturation requirements of B cell lines that lead to their production. Passive immunization with bnAbs provides efficient, cross-clade protection against simian/human immunodeficiency chimeric virus (SHIV) challenges in nonhuman primates. Despite many efforts to design immunogens that elicit them by active immunization, no immunogen other than HIV itself has yet been able to elicit a bnAb response. For this reason, innovative approaches are under investigation, including their production in the body through a gene delivery approach, vector immunoprophylaxis. © 2013 Elsevier Ltd. Source

Girard M.P.,French National Academy of Medicine | Katz J.M.,Centers for Disease Control and Prevention | Pervikov Y.,Initiative for Vaccine Research | Hombach J.,Initiative for Vaccine Research | Tam J.S.,Initiative for Vaccine Research
Vaccine | Year: 2011

On February 17-18, 2011, the World Health Organization convened the 7th meeting on " The Evaluation of Pandemic Influenza Vaccines in Clinical Trials" to review the progress made on pandemic A (H1N1) 2009 vaccines and the evaluation of their effectiveness in the field, especially in children less than 3 years of age and in pregnant women. Other topics to be addressed included a comparison of egg- and cell culture-based influenza vaccines, technical issues related to vaccine strain development and vaccine potency, and the status of development of prototype influenza vaccines using new technologies. Pandemic A (H1N1) vaccines were safe in young children, pregnant women and immunocompromized individuals. Overall effectiveness of inactivated A (H1N1) vaccines for all ages was found to vary between 72% and 100% in different countries and with different vaccine preparations. Effectiveness of pandemic A (H1N1) 2009 live attenuated vaccine was estimated to be approximately 80% in pediatric populations in the USA. A single dose of inactivated vaccine adjuvanted with AS03, MF59 or AF03 induced protective immunity in young children and pregnant women. However, unadjuvanted vaccines as well as low dose adjuvanted vaccines (1.9 μg HA) required two doses to elicit protective antibody levels in these populations. Clinical trials of influenza vaccines developed using new technologies showed they were well tolerated and induced antibody and/or T cell immune responses to viral proteins. Further studies are warranted to validate novel immunological criteria for evaluation and licensing of such new influenza vaccine concepts. On the regulatory side, work should be undertaken to harmonize the results of serological tests used to evaluate the immunogenicity of traditional influenza vaccines. © 2011. Source

Girard M.P.,French National Academy of Medicine | Plotkin S.A.,University of Pennsylvania
Current Opinion in HIV and AIDS | Year: 2012

Purpose of review: To review the status of HIV vaccine development Recent findings: Since the discovery of HIV-1 in the early 1980s considerable effort has been exerted to develop a prophylactic vaccine, with relatively meagre results. The absence of natural immunity has proven to be a major stumbling block in identifying a mechanism of protection. However, many different animal models have contributed to our knowledge of the pathogenesis of infection and of the variety of antibody and cellular responses that are induced by the virus. The knowledge created by the studies in nonhuman primates, although important, has not necessarily been proven applicable in humans and thus an effective vaccine has been elusive. The combined lack of a fully predictive animal model ('mice lie and monkeys exaggerate') and lack of defined markers of immune protection against HIV-1 necessitate that HIV vaccines be tested directly for efficacy in phase IIb/III efficacy trials in human volunteers at risk. A trial conducted in Thailand showed moderate but significant protection against infection. Summary: The process of HIV vaccine development is slow, costly and tedious. However, recent preclinical and clinical results have fortunately been a source of renewed optimism in the field. © 2011 Wolters Kluwer Health. Source

Girard M.P.,French National Academy of Medicine | Katz J.,Centers for Disease Control and Prevention | Pervikov Y.,World Health Organization | Palkonyay L.,World Health Organization | Kieny M.-P.,World Health Organization
Vaccine | Year: 2010

On February 17-18, 2010, the World Health Organization (WHO) convened the 6th meeting on the " Evaluation of pandemic influenza vaccines in clinical trials" to review the progress made on new A (H1N1) 2009 vaccines and prototype H5N1 vaccines and their evaluation in clinical trials. A number of vaccine types were reviewed, including classical egg-derived and cell culture-derived inactivated vaccines, such as split virus or whole-virion vaccines, and live-attenuated vaccines (LAIV), as well as vaccines developed using new technologies. The amount of antigen needed, the effect of adjuvants and the number of doses required to induce adequate antibody responses in various populations, together with the issue of safety of the vaccines, were major topics of the meeting. The effectiveness of H1N1 vaccines and the need for standardization of vaccine potency tests were also discussed. Independent of the vaccine type and the presence or absence of an adjuvant, all A (H1N1) 2009 vaccines were well tolerated, eliciting only mild to moderate local or systemic reactions. For most vaccines tested, a single dose was sufficient to elicit a potentially protective antibody response in the majority of vaccinees >10 years of age. However, a second dose of vaccine was needed to boost immune responses in infants and toddlers 6 months to 3 years of age and, with some vaccines, in children aged 3-9 years. © 2010 World Health Organization. Source

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