Marc P Girard

Publications of Marc P Girard

• HIV vaccine development at the turn of the 21st century.

  Authors: Marc P Girard, Stanley A Plotkin

  Current opinion in HIV and AIDS. 11/2011; 7(1):4-9.

  To review the status of HIV vaccine development Since the discovery of HIV-1 in the early 1980s considerable effort has been exerted to develop a prophylactic vaccine, with relatively meagre results.To review the status of HIV vaccine development 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. 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.

• Report of the 7th meeting on Evaluation of Pandemic Influenza Vaccines in Clinical Trials, World Health Organization, Geneva, 17-18 February 2011.

  Authors: Marc P Girard, Jacqueline M Katz, Yuri Pervikov, Joachim Hombach, John S Tam

  Vaccine. 08/2011; 29(44):7579-86.

  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)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.

• Human immunodeficiency virus (HIV) immunopathogenesis and vaccine development: a review.

  Authors: Marc P Girard, Saladin Osmanov, Olga M Assossou, Marie-Paule Kieny

  Vaccine. 06/2011; 29(37):6191-218.

  The development of a safe, effective and globally affordable HIV vaccine offers the best hope for the future control of the HIV-1 pandemic. Since 1987, scores of candidate HIV-1 vaccines have beenThe development of a safe, effective and globally affordable HIV vaccine offers the best hope for the future control of the HIV-1 pandemic. Since 1987, scores of candidate HIV-1 vaccines have been developed which elicited varying degrees of protective responses in nonhuman primate models, including DNA vaccines, subunit vaccines, live vectored recombinant vaccines and various prime-boost combinations. Four of these candidate vaccines have been tested for efficacy in human volunteers, but, to the exception of the recent RV144 Phase III trial in Thailand, which elicited a modest but statistically significant level of protection against infection, none has shown efficacy in preventing HIV-1 infection or in controlling virus replication and delaying progression of disease in humans. Protection against infection was observed in the RV144 trial, but intensive research is needed to try to understand the protective immune mechanisms at stake. Building-up on the results of the RV144 trial and deciphering what possibly are the immune correlates of protection are the top research priorities of the moment, which will certainly accelerate the development of an highly effective vaccine that could be used in conjunction with other HIV prevention and treatment strategies. This article reviews the state of the art of HIV vaccine development and discusses the formidable scientific challenges met in this endeavor, in the context of a better understanding of the immunopathogenesis of the disease.

• Report of the 6th meeting on the evaluation of pandemic influenza vaccines in clinical trials World Health Organization, Geneva, Switzerland, 17-18 February 2010.

  Authors: Marc P Girard, Jacqueline Katz, Yuri Pervikov, Laszlo Palkonyay, Marie-Paule Kieny

  Vaccine. 10/2010; 28(42):6811-20.

  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)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.

• The 2009 A (H1N1) influenza virus pandemic: A review.

  Authors: Marc P Girard, John S Tam, Olga M Assossou, Marie Paule Kieny

  Vaccine. 07/2010; 28(31):4895-902.

  In March and early April 2009 a new swine-origin influenza virus (S-OIV), A (H1N1), emerged in Mexico and the USA. The virus quickly spread worldwide through human-to-human transmission. In view ofIn March and early April 2009 a new swine-origin influenza virus (S-OIV), A (H1N1), emerged in Mexico and the USA. The virus quickly spread worldwide through human-to-human transmission. In view of the number of countries and communities which were reporting human cases, the World Health Organization raised the influenza pandemic alert to the highest level (level 6) on June 11, 2009. The propensity of the virus to primarily affect children, young adults and pregnant women, especially those with an underlying lung or cardiac disease condition, and the substantial increase in rate of hospitalizations, prompted the efforts of the pharmaceutical industry, including new manufacturers from China, Thailand, India and South America, to develop pandemic H1N1 influenza vaccines. All currently registered vaccines were tested for safety and immunogenicity in clinical trials on human volunteers. All were found to be safe and to elicit potentially protective antibody responses after the administration of a single dose of vaccine, including split inactivated vaccines with or without adjuvant, whole-virion vaccines and live-attenuated vaccines. The need for an increased surveillance of influenza virus circulation in swine is outlined.

• Mucosal immunity and HIV/AIDS vaccines Report of an International Workshop, 28-30 October 2007.

  Authors: Marc P Girard, Geetha P Bansal, Livia Pedroza-Martins, Betty Dodet, Vijay Mehra, Marco Schito, Bonnie Mathieson, Jean-François Delfraissy, James Bradac

  Vaccine. 08/2008; 26(32):3969-77.

  In October 2007, a joint ANRS-NIH workshop was held on "Mucosal immunity and HIV/AIDS vaccines" in Veyrier-du-Lac, France. Goal of the meeting was to discuss recent developments in the understandingIn October 2007, a joint ANRS-NIH workshop was held on "Mucosal immunity and HIV/AIDS vaccines" in Veyrier-du-Lac, France. Goal of the meeting was to discuss recent developments in the understanding of viral entry and dissemination at mucosal surfaces, rationale for designing vaccines to elicit mucosal immune responses by various routes of immunization, and the types of immune responses elicited. Lessons were drawn from existing vaccines against viral mucosal infections, from the recent failure of the Merck Ad5/HIV vaccine and from attempts at mucosal immunization against SIV. This report summarizes the main concepts and conclusions that came out of the meeting.

• Report of the third meeting on "influenza vaccines that induce broad spectrum and long-lasting immune responses", World Health Organization, Geneva, Switzerland, 3-4 December 2007.

  Authors: Marc P Girard, Albert Osterhaus, Yuri Pervikov, Laszlo Palkonyay, Marie Paule Kieny

  Vaccine. 06/2008; 26(20):2443-50.

• HIV/AIDS vaccines: a need for new concepts?

  Authors: Marc P Girard, Geetha P Bansal

  International reviews of immunology. 02/2008; 27(6):447-71.

  HIV vaccine research is at a crossroads carefully contemplating on the next path. The unexpected results of the Merck vaccine trial, while providing a stunning blow to a field in dire need of aHIV vaccine research is at a crossroads carefully contemplating on the next path. The unexpected results of the Merck vaccine trial, while providing a stunning blow to a field in dire need of a protective vaccine, has also raised several fundamental questions regarding the candidate immunogen itself, preexisting immunity to vaccine vectors, surrogate assays and animal models used for assessing preclinical protective responses, as well as relevant endpoints to be measured in a clinical trial. As a result, the research community is faced with the daunting task of identifying novel vaccine concepts and products to continue the search. This review highlights and addresses some of the scientific and practical concerns.

• A review of human vaccine research and development: malaria.

  Authors: Marc P Girard, Zarifah H Reed, Martin Friede, Marie Paule Kieny

  Vaccine. 03/2007; 25(9):1567-80.

  The last several years have seen significant progress in the development of vaccines against malaria. Most recently, proof-of-concept of vaccine-induced protection from malaria infection and diseaseThe last several years have seen significant progress in the development of vaccines against malaria. Most recently, proof-of-concept of vaccine-induced protection from malaria infection and disease was demonstrated in African children. Pursued by various groups and on many fronts, several other candidate vaccines are in early clinical trials. Yet, despite the optimism and promise, an effective malaria vaccine is not yet available, in part because of the lack of understanding of the types of immune responses needed for protection, added to the difficulty of identifying, selecting and producing the appropriate protective antigens from a parasite with a genome of well over five thousand genes and to the frequent need to enhance the immunogenicity of purified antigens through the use of novel adjuvants or delivery systems. Insufficient clinical trial capacity and normative research functions such as local ethical committee reviews also contribute to slow down the development process. This article attempts to summarize the state of the art of malaria vaccine development.

• A review of vaccine research and development: the human immunodeficiency virus (HIV).

  Authors: Marc P Girard, Saladin K Osmanov, Marie Paule Kieny

  Vaccine. 06/2006; 24(19):4062-81.

  Since the discovery of AIDS in 1981, the global spread of HIV has reached pandemic proportions, representing a global developmental and public health threat. The development of a safe, globallySince the discovery of AIDS in 1981, the global spread of HIV has reached pandemic proportions, representing a global developmental and public health threat. The development of a safe, globally effective and affordable HIV vaccine offers the best hope for the future control of the pandemic. Significant progress has been made over the past years in the areas of basic virology, immunology, pathogenesis of HIV/AIDS and the development of antiretroviral drugs. However, the development of an HIV vaccine faces formidable scientific challenges related to the high genetic variability of the virus, the lack of immune correlates of protection, limitations with the existing animal models and logistical problems associated with the conduct of multiple clinical trials. More than 35 vaccine candidates have been tested in Phase I/II clinical trials, involving more than 10,000 volunteers, and two Phase III trials have been completed, themselves involving more than 7500 volunteers. Multiple vaccine concepts and vaccination strategies have been tested, including DNA vaccines, subunit vaccines, live vectored recombinant vaccines and various prime-boost vaccine combinations. This article reviews the state of the art in HIV vaccine development, summarizes the results obtained so far and discusses the challenges to be met in the development of the various vaccine candidates.

• A review of vaccine research and development: meningococcal disease.

  Authors: Marc P Girard, Marie-Pierre Preziosi, Maria-Teresa Aguado, Marie Paule Kieny

  Vaccine. 06/2006; 24(22):4692-700.

  This paper reviews the current status of research and development of vaccines against meningococcal disease due to Neisseria meningitidis, a major cause of severe meningitis and septicemia withThis paper reviews the current status of research and development of vaccines against meningococcal disease due to Neisseria meningitidis, a major cause of severe meningitis and septicemia with epidemic potential. While five serogroups (A, B, C, Y, and W135) are responsible for most of the disease, Group A remains unique in its ability to cause large scale epidemics mainly in Africa but also in Asia. The majority of cases in Europe and America are due to Groups B and C. The successful experience with Hib and pneumococcal conjugate vaccines has paved the way for the development of polysaccharide conjugate vaccines for the prevention of meningococcal disease. Widespread vaccination with Group C conjugate vaccines now in use in several European countries indicates that these vaccines are immunogenic, induce immunological memory, reduce colonization and provide herd immunity to the general population. A monovalent group A conjugate vaccine being developed at an affordable price, offers hope for the elimination of large epidemics in African countries. Multivalent (A, C, Y, W) conjugate vaccines are being developed, and one has already been licensed. However, effective global prevention of meningococcal disease will not be achievable without the development of a vaccine against Group B meningitis, for which outer membrane protein vaccines are under development.

• A review of vaccine research and development: human enteric infections.

  Authors: Marc P Girard, Duncan Steele, Claire-Lise Chaignat, Marie Paule Kieny

  Vaccine. 04/2006; 24(15):2732-50.

  Worldwide, enteric infections rank third among all causes of disease burden, being responsible for some 1.7-2.5 million deaths per year, mostly in young children and infants in developing countries.Worldwide, enteric infections rank third among all causes of disease burden, being responsible for some 1.7-2.5 million deaths per year, mostly in young children and infants in developing countries. The main infectious agents responsible for human enteric infections include several viruses (enteric adenoviruses, astroviruses, human caliciviruses (HuCV), rotaviruses (RV)) and several bacterial agents, such as Campylobacter jejuni, a variety of pathogenic Escherichia coli strains including enterotoxigenic E. coli (ETEC), several Shigella species, various Salmonella strains including S. typhi and S. paratyphi, the agents of typhoid fever, and Vibrio cholerae, the agent of cholera. While effective vaccines are available at present against typhoid fever and cholera, no vaccine is available against illnesses caused by HuCV, Campylobacter, ETEC or the Shigellae. Rotavirus vaccines have had more success, although RV disease prevention suffered a major setback in 1999 with the withdrawal of a live simian-human reassortant RV vaccine less than a year after its introduction. New live oral RV vaccines have now been developed and are or should presently be ready for licensure. This article reviews the state of the art in vaccine R&D against human viral and bacterial enteric infections of public health importance.

• A review of vaccine research and development: tuberculosis.

  Authors: Marc P Girard, Uli Fruth, Marie Paule Kieny

  Vaccine. 01/2006; 23(50):5725-31.

  Substantial progress has been made during the past 15 years towards the development of improved vaccines for tuberculosis. This is due to advances in the characterization of genes and antigens ofSubstantial progress has been made during the past 15 years towards the development of improved vaccines for tuberculosis. This is due to advances in the characterization of genes and antigens of Mycobacterium tuberculosis (M. tb), aided by the availability of genome sequences of different mycobacterial species and M. tb isolates and to greater understanding of protective immune responses to the pathogen in both animals and humans. More than one hundred candidate vaccines have been tested in animal models, representing all of the major vaccine design strategies, and some have now moved into clinical trials. This review summarizes recent advances in tuberculosis vaccine development.

• A review of vaccine research and development: human acute respiratory infections.

  Authors: Marc P Girard, Thomas Cherian, Yuri Pervikov, Marie Paule Kieny

  Vaccine. 01/2006; 23(50):5708-24.

  Worldwide, acute respiratory infections (ARIs) constitute the leading cause of acute illnesses, being responsible for nearly 4 million deaths every year, mostly in young children and infants inWorldwide, acute respiratory infections (ARIs) constitute the leading cause of acute illnesses, being responsible for nearly 4 million deaths every year, mostly in young children and infants in developing countries. The main infectious agents responsible for ARIs include influenza virus, respiratory syncytial virus (RSV), parainfluenza virus type 3 (PIV-3), Streptococcus pneumoniae and Haemophilus influenzae. While effective vaccines against influenza, H. influenzae type b (Hib) and S. pneumoniae infections have been available for several years, no vaccine is available at present against illnesses caused by RSV, PIV-3, metapneumovirus or any of the three novel coronaviruses. In addition, the threat constituted by the multiple outbreaks of avian influenza during the last few years is urgently calling for the development of new influenza vaccines with broader spectrum of efficacy, which could provide immunity against an avian influenza virus pandemic. This article reviews the state of the art in vaccine R&D against ARIs and attempts to address these basic public health questions.

• Human vaccine research and development: an overview.

  Authors: Marie Paule Kieny, Marc P Girard

  Vaccine. 01/2006; 23(50):5705-7.

  One-fifth of global mortality, especially in children under the age of five is due to infectious diseases. Vaccines are effective at combating these diseases, as shown by the success of smallpoxOne-fifth of global mortality, especially in children under the age of five is due to infectious diseases. Vaccines are effective at combating these diseases, as shown by the success of smallpox eradication, the impressive progress towards polio eradication, the significant achievements in measles mortality reduction and many others. New safe and effective vaccines must be developed for a variety of infections of public health importance against which no effective preventive intervention measure is either available or practical. In addition, appropriate mechanisms should be put in place to ensure access for all children to the needed vaccines. To meet these challenges, a new paradigm needs to be built among all stakeholders of immunization, including countries, industry, research institutions, foundations and international agencies like the World Health Organization (WHO) and the United Nations Children Fund (UNICEF). Importantly, developing countries should be empowered to participate actively in the development and introduction of new vaccines according to their national priorities.

• [The quest for an HIV vaccine]

  Authors: Marc P Girard

  Bulletin de l'Académie nationale de médecine. 06/2005; 189(5):831-44; discussion 844.

  At least 49 phase I trials of candidate vaccines for HIV/AIDS, together with two phase II trials and two phase III trials have been completed since the mid 1980s, involving more than 35 differentAt least 49 phase I trials of candidate vaccines for HIV/AIDS, together with two phase II trials and two phase III trials have been completed since the mid 1980s, involving more than 35 different vaccine formulations, 14 different adjuvants and more than 12000 volunteers. Although several neutralizing epitopes have been identified on the surface of the virus glycoprotein spikes, the goal of an HIV envelope-based vaccine capable of eliciting broadly reactive neutralizing antibodies is elusive. A gp120-based vaccine, which was tested in two phase III trials (one in the USA and the other in Thailand), was found to have no protective efficacy when injected every 6 months. The observation that, in the monkey model, both viremia (virus load) and clinical outcome are controlled by the CD8+ T cell response, prompted the development of an array of candidate vaccines capable of inducing HIV-specific T cell responses. A series of HIV vaccines based on live virus vectors are already undergoing clinical studies, including a live recombinant canarypox virus vaccine (ALVAC), which is in phase III trials in Thailand, a non-replicative adenovirus type 5 (Ad5) vaccine, which is entering a phase II trial in the USA and the Caribbean, and live recombinant vaccines based on the attenuated vaccinia virus MVA vector, which have already completed several phase I studies, used either alone or combined with DNA vaccine priming. A whole array of other vaccines based on live vectors, DNA, peptides and other designs, are being tested in nonhuman primates. None of these vaccines has been able to prevent infection following experimental challenge, but all were found to control viral load and to prevent CD4 cell loss. T cell-stimulating vaccines are thus unable to prevent infection but prevent or slow disease progression by controlling virus replication. Their efficacy in humans remains to be determined.

• Mucosal immunity and HIV/AIDS vaccines: Report of an International Workshop, 28–30 October 2007

  Authors: Marc P. Girard, Geetha P. Bansal, Livia Pedroza-Martins, Betty Dodet, Vijay Mehra, Marco Schito, Bonnie Mathieson, Jean-François Delfraissy, James Bradac

  Vaccine.

  In October 2007, a joint ANRS-NIH workshop was held on “Mucosal immunity and HIV/AIDS vaccines” in Veyrier-du-Lac, France. Goal of the meeting was to discuss recent developments in the understandingIn October 2007, a joint ANRS-NIH workshop was held on “Mucosal immunity and HIV/AIDS vaccines” in Veyrier-du-Lac, France. Goal of the meeting was to discuss recent developments in the understanding of viral entry and dissemination at mucosal surfaces, rationale for designing vaccines to elicit mucosal immune responses by various routes of immunization, and the types of immune responses elicited. Lessons were drawn from existing vaccines against viral mucosal infections, from the recent failure of the Merck Ad5/HIV vaccine and from attempts at mucosal immunization against SIV. This report summarizes the main concepts and conclusions that came out of the meeting.

• The 2009 A (H1N1) influenza virus pandemic: A review

  Authors: Marc P. Girard, John S. Tam, Olga M. Assossou, Marie Paule Kieny

  Vaccine.

  In March and early April 2009 a new swine-origin influenza virus (S-OIV), A (H1N1), emerged in Mexico and the USA. The virus quickly spread worldwide through human-to-human transmission. In view ofIn March and early April 2009 a new swine-origin influenza virus (S-OIV), A (H1N1), emerged in Mexico and the USA. The virus quickly spread worldwide through human-to-human transmission. In view of the number of countries and communities which were reporting human cases, the World Health Organization raised the influenza pandemic alert to the highest level (level 6) on June 11, 2009. The propensity of the virus to primarily affect children, young adults and pregnant women, especially those with an underlying lung or cardiac disease condition, and the substantial increase in rate of hospitalizations, prompted the efforts of the pharmaceutical industry, including new manufacturers from China, Thailand, India and South America, to develop pandemic H1N1 influenza vaccines. All currently registered vaccines were tested for safety and immunogenicity in clinical trials on human volunteers. All were found to be safe and to elicit potentially protective antibody responses after the administration of a single dose of vaccine, including split inactivated vaccines with or without adjuvant, whole-virion vaccines and live-attenuated vaccines. The need for an increased surveillance of influenza virus circulation in swine is outlined.

• Report of the 6th meeting on the evaluation of pandemic influenza vaccines in clinical trials World Health Organization, Geneva, Switzerland, 17–18 February 2010

  Authors: Marc P. Girard, Jacqueline Katz, Yuri Pervikov, Laszlo Palkonyay, Marie-Paule Kieny

  Vaccine.

  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)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.