[From vaccine manufacturing to its availability in pharmacy]. / De la fabrication d'un vaccin à sa mise à disposition en pharmacie.

After a brief overview of vaccine industry and the regulatory requirements for biologics, the biological and pharmaceutical manufacturing of vaccine is presented. Vaccine production specificities are discussed. They show that, despite recent efforts and progress, continuously adapting vaccine supply to demand "at any time and in any place" remains a challenge, for reasons inherent in biological production, which is a production in tight flow, structurally delicate (control of the biological hazard), and weakly reactive.

[Update on vaccine research. Proceedings of the 15th annual conference on vaccine research organized by the National Foundation for Infectious Diseases]. / Actualités en matière de recherche vaccinale. Compte-rendu de la 15(e) conférence annuelle sur la recherche vaccinale organisée par la National Foundation for Infectious Diseases.

Every year, the National Foundation for Infectious Diseases brings together more than 300 participants to review progress in vaccine research and development and identify the most promising avenues of research. These conferences are among the most important scientific meetings entirely dedicated to vaccine research for both humans and animals, and provide a mix of plenary sessions with invited presentations by acknowledged international experts, parallel sessions, poster sessions, and informal exchanges between experts and young researchers. During the Fifteenth Conference that took place in Baltimore in May 2012, various topics were addressed, including the scientific basis for vaccinology; exploration of the immune response; novel vaccine design; new adjuvants; evaluation of the impact of newly introduced vaccines (such as rotavirus, HPV vaccines); vaccine safety; and immunization strategies. The new techniques of systems biology allow for a more comprehensive approach to the study of immune responses in order to identify correlates of protection and to design novel vaccines against chronic diseases such as AIDS or malaria, against which natural immunity is incomplete.

[Current events in vaccination]. / Actualités en matière de vaccination.

The annual meeting of the Infectious Disease Society of America (IDSA) ; which brought together nearly 5000 participants from over 80 countries in Vancouver, Canada, October 21 to 24, 2010 ; provided a review of the influenza (H1N1) 2009 pandemic, evaluated vaccination programmes and presented new vaccines under development. With 12,500 deaths in the United States in 2009-2010, the influenza (H1N1) 2009 pandemic was actually less deadly than the seasonal flu. But it essentially hit the young, and the toll calculated in years of life lost is high. The monovalent vaccines, whether live attenuated or inactivated with or without adjuvants, were well tolerated in toddlers, children, adults and pregnant women. In order to protect infants against pertussis, family members are urged to get their booster shots. The introduction of the 13-valent Pneumococcal conjugated vaccine in the beginning of 2010 may solve - but for how long ? - the problem of serotype replacement, responsible for the re-increasing incidence of invasive Pneumococcal infections observed in countries that had introduced the 7-valent vaccine. The efficacy of a rotavirus vaccine has been confirmed, with a reduction in hospitalization in the United States and a reduction in gastroenteritis-related deaths in Mexico. In the United States, vaccination of pre-adolescents against human papillomavirus (HPV) has not resulted in any specific undesirable effects. Routine vaccination against chicken pox, recommended since 1995, has not had an impact on the evolution of the incidence of shingles. Vaccination against shingles, recommended in the United States for subjects 60 years and over, shows an effectiveness of 55 %, according to a cohort study (Kaiser Permanente, Southern California). Although some propose the development of personalized vaccines according to individual genetic characteristics, the priority remains with increasing vaccine coverage, not only in infants but also in adults and the elderly. Vaccine calendars that cover a whole lifetime should be promoted, since the vaccination of adults and seniors is a determining factor of good health at all ages.

Human papillomavirus (HPV) vaccination: perception and practice among French general practitioners in the year since licensing.

Acceptance of the Human Papillomavirus (HPV) vaccine by targeted populations will depend to a large extent on its acceptability among physicians. We examined the perceptions, attitudes and practices of general practitioners (GPs) in relation to HPV vaccination. From November 2007 to April 2008, a cross-sectional survey was carried out among a representative 5% sample of GPs in the large Rhône-Alpes region of France. Both quantitative (self-administered questionnaire) and qualitative (interview) approaches were used. During the month preceding the survey, 75.6% of the 279 GPs who responded had given at least one HPV vaccination and 47.6% had given a vaccination at the routine target age of 14 years. Overall, 80.8% of GPs reported a favourable opinion about HPV vaccination, 17.4% were uncertain and 1.8% were opposed. The main justification for a favourable opinion related to the public health benefits of the HPV vaccination (cited by 60% of those favouring vaccination). The main justification for an "opposed or uncertain" opinion was the too recent introduction of the vaccine (cited by 43.4%). The major difficulties in providing HPV vaccination were patients' concerns about potential side effects (cited by 37% of the respondents) and the target age of 14 years (28.9%). Interviews suggested that the concern about age may relate to the need, as perceived by GPs, to discuss sexually transmitted infections with adolescent patients. A favourable opinion about HPV vaccination was associated with seeing more female patients per week, younger age, and GPs' intention to recommend hepatitis B vaccination. This representative survey of GPs in a major region of France finds a favourable opinion about the HPV vaccine and widespread use of it, despite some concerns that the recent introduction of the vaccine means that we do not yet fully understand the potential for side effects and about the recommended target age of recipients.

[Current events in vaccination]. / Actualités en matière de vaccination.

The annual meeting of the Infectious Disease Society of America (IDSA); which brought together nearly 5000 participants from over 80 countries in Vancouver, Canada, October 21 to 24, 2010; provided a review of the influenza (H1N1) 2009 pandemic, evaluated vaccination programmes and presented new vaccines under development. With 12,500 deaths in the United States in 2009-2010, the influenza (H1N1) 2009 pandemic was actually less deadly than the seasonal flu. But it essentially hit the young, and the toll calculated in years of life lost is high. The monovalent vaccines, whether live attenuated or inactivated with or without adjuvants, were well tolerated in toddlers, children, adults and pregnant women. In order to protect infants against pertussis, family members are urged to get their booster shots. The introduction of the 13-valent Pneumococcal conjugated vaccine in the beginning of 2010 may solve--but for how long?--the problem of serotype replacement, responsible for the re-increasing incidence of invasive Pneumococcal infections observed in countries that had introduced the 7-valent vaccine. The efficacy of a rotavirus vaccine has been confirmed, with a reduction in hospitalization in the United States and a reduction in gastroenteritis-related deaths in Mexico. In the United States, vaccination of pre-adolescents against human papillomavirus (HPV) has not resulted in any specific undesirable effects. Routine vaccination against chicken pox, recommended since 1995, has not had an impact on the evolution of the incidence of shingles. Vaccination against shingles, recommended in the United States for subjects 60 years and over, shows an effectiveness of 55%, according to a cohort study (Kaiser Permanente, Southern California). Although some propose the development of personalized vaccines according to individual genetic characteristics, the priority remains with increasing vaccine coverage, not only in infants but also in adults and the elderly. Vaccine calendars that cover a whole lifetime should be promoted, since the vaccination of adults and seniors is a determining factor of good health at all ages.

[Distribution of neutralizing measles serum antibodies according to age in women of childbearing age in France in 2005-2006]. / Distribution en fonction de l'âge de la concentration sérique des anticorps neutralisants antirougeole chez les femmes en âge de procréer en France en 2005-2006.

UNLABELLED: Measles-vaccine coverage (MVC) increased significantly only beginning in 1983 based on the official recommendations. The majority of women born after 1983 should have vaccine-acquired rather than naturally derived immunity. Passively transferred measles antibodies (Mab) are expected to provide protection to offsprings during their 1st few months of life. OBJECTIVE: Compare neutralizing Mab titers according to age in women aged 12-40 years, i.e., born before and after 1983. METHODS: A multicenter seroepidemiological study was conducted in France in 2005-2006; 210 outpatient or hospitalized women were enrolled and classified into 4 age groups (12-18, 19-22, 23-30, and 31-40 years). Mab titers were assessed using a reference plaque reduction neutralization assay (protection threshold > 120 mIU/ml). RESULTS: Ninety-four percent of subjects had a Mabs titer greater than 120 mIU/ml. Women born before 1983 had significantly higher geometric mean titers (GMTs) of Mabs than those born after 1983(1358 mIU/ml vs. 731 mIU/ml [p<0.001]). The comparison of the 4 cohorts showed a significant decrease (p<0.001) in GMTs of Mab in the female population with increasing age (670, 771, 1173, and 1821 mUI/ml, respectively, in the 12-18, 19-22, 23-30, and 31-40 years age groups). For the 1st time in France, we show in women of childbearing age that in 2005-2006 neutralizing Mab GMTs were far above protective threshold for all age groups. Women in younger age groups (with high MVC) have significantly lower Mab titers. A lower passive transfer of Mab to their offsprings could result in a shorter period of measles protection and question the measles vaccine 1st dose at 1 year.

Paediatric varicella hospitalisations in France: a nationwide survey.

Paediatric patients hospitalised with varicella (n = 1575) were reported to a French national network between March 2003 and July 2005. Superinfection was identified in 50.3% of cases, principally of skin and soft-tissue (36.5%). The risk of superinfection increased with fever relapse, use of non-steroidal anti-inflammatory drugs, prolonged fever, an age of 1-5 years, and contamination at the childminder's home. Neurological complications were observed in 7.8% of cases, while pulmonary complications were less frequent (3.1%). Forty-nine patients had sequelae and eight patients died. Surveillance should continue in France with a view to the future implementation of a universal vaccination programme.

[WITHDRAWN: Vaccination against human papillomavirus: a new vaccination for the female adolescent?] / WITHDRAWN: La vaccination contre les papillomavirus humains : une nouvelle vaccination pour l'adolescente ?

Ahead of Print article withdrawn by publisher.

[35-year measles, mumps, rubella vaccination assessment in France]. / Evaluation de 35 années de vaccination rougeole-oreillons-rubéole en France.

AIM: The setting-up and the follow-up of a vaccination programme require important human and economical investments. Our study objective consists of the clinical benefit evaluation given by measles, mumps and rubella (MMR) vaccination since monovalent and combined vaccines availability (35 years for measles, 30 years for rubella and 20 years for mumps). METHOD: Vaccination impact has been evaluated from the modelisation for each disease under the shape of a decision tree relying on epidemiological data and on efficacy data of the vaccines. We have compared the results in terms of complications, sequaela, deaths in the vaccinated population (vaccination period) with the results that we would obtain if this same population had not been vaccinated (non vaccination period). The general model was applied to each of the three diseases excluding congenital rubella syndrome. They have been modelised according to the occurrence, or not, of a complication leading to an evolution towards either recovery or sequaela or death. The estimation of the number of avoided congenital rubella syndromes has been made from the number of protected women by vaccination and incidence figures of congenital rubella syndromes reported in the population considered before and after vaccination. RESULTS: In France over the period of time considered, almost 2 million meningitis, 60 000 encephalitis, 170 subacute sclerosis panencephalitis and more than 5600 neurological sequaela including more than 600 deafness cases have been avoided as a result of the MMR vaccination programme. Moreover, 590 000 pneumonia, more than one million of acute otitis media and 300 000 orchitis, 3000 rubella infection cases occurring during pregnancy have also been avoided. Overall, more than 12 000 deaths that have been avoided as a result of the MMR vaccination. CONCLUSIONS: In France, MMR vaccination programme leads to a huge benefit in terms of public health, which emphasises the true value of vaccination in the daily medical practice.

[Central nervous system demyelinating disease following hepatitis B vaccination with GenHevac B. Review of ten years of spontaneous notifications (1989-1998)]. / Pathologies démyélinisantes du système nerveux central rapportées après vaccination hépatite B par GenHevac B. Bilan de dix années de notifications spontanées (1989-1998).

OBJECTIVES: To describe and analyze spontaneous reports of central nervous system (CNS) demyelinating disease including multiple sclerosis, following vaccination with GenHevac B vaccine, from 1989 to December 31, 1998. METHODS: Descriptive analysis of adverse event reports in the vaccinated population, including the number of cases of CNS demyelinating disease, their frequencies, their dates of onset in relation to dates of report and their distribution according to age, sex and the number of injections. A Kaplan-Meier curve was used to analyze the time period between the last dose of vaccine and the onset of CNS demyelinating disease. RESULTS: Overall, 187 cases of CNS demyelinating disease were spontaneously reported, (0.54 reports per 100,000 doses of GenHevac B distributed). The average time period between the occurring date of onset of the disease and its subsequent report was 24 months. The average age of onset was 31.7 years old and 73% of cases were women. The time between the last dose of vaccine and the onset of disease was regularly distributed from 1 day to 5 years (median: 60 days). CONCLUSION: These results, together with available clinical, epidemiological data regarding multiple sclerosis, do not suggest a causal relationship between CNS demyelinating disease and vaccination with GenHevac B.