An expert panel opinion on protection against pertussis in Mexico: The role of acellular and whole-cell vaccines.

Pertussis is a highly contagious disease caused by Bordetella pertussis, which may be preventable by vaccination. There are two types of vaccines: whole-cell vaccines and acellular vaccines. Since pertussis control worldwide is heterogeneous, re-emergence of whooping cough has been observed in some countries. This re-emergence has been related to several factors: increased susceptibility to infection, better detection of disease, problems in obtaining adequate vaccination coverage, increase in susceptible subjects (mainly under 6 months of age), loss of immunity in adolescents and young adults, and likely genetic and adaptive B. pertussis changes. This paper discusses whole-cell and acellular vaccines' characteristics, advantages, and disadvantages. International recommendations are presented, and the participants' position is offered regarding the influence of the use of acellular vaccines and the potential disadvantages of reintroducing whole-cell vaccines, mainly due to their reactogenicity. Finally, strategies to achieve better control of pertussis in Mexico are discussed.

La tos ferina es una enfermedad causada por Bordetella pertussis. Aunque es altamente contagiosa, puede ser prevenible por vacunación. Existen dos tipos de vacunas: las de células enteras y las acelulares. La tos ferina ha resurgido en algunos países debido a que su control a escala mundial es heterogéneo. Esta reemergencia se ha relacionado con diversos factores: mayor sensibilidad hacia la infección, mejor detección de la enfermedad, problemas para obtener adecuadas coberturas de vacunación, incremento en los sujetos susceptibles (especialmente menores de 6 meses), pérdida de la inmunidad en los adolescentes y adultos jóvenes, y probables cambios genéticos y adaptativos de B. pertussis. En este documento se analizan las características, las ventajas y las desventajas de las vacunas de células enteras y de las vacunas acelulares. Se presentan las recomendaciones internacionales y se ofrece el posicionamiento de los participantes con respecto a la influencia del uso de vacunas acelulares y las desventajas potenciales de volver a utilizar vacunas de células enteras, en especial por su reactogenicidad. Por último, se analizan las estrategias para lograr un mejor control de la tos ferina en México.

Opinión de un panel de expertos sobre la protección contra la tos ferina en México: el papel de las vacunas acelulares y de células enteras / An expert panel opinion on protection against pertussis in Mexico: The role of acellular and whole-cell vaccines

Resumen La tos ferina es una enfermedad causada por Bordetella pertussis. Aunque es altamente contagiosa, puede ser prevenible por vacunación. Existen dos tipos de vacunas: las de células enteras y las acelulares. La tos ferina ha resurgido en algunos países debido a que su control a escala mundial es heterogéneo. Esta reemergencia se ha relacionado con diversos factores: mayor sensibilidad hacia la infección, mejor detección de la enfermedad, problemas para obtener adecuadas coberturas de vacunación, incremento en los sujetos susceptibles (especialmente menores de 6 meses), pérdida de la inmunidad en los adolescentes y adultos jóvenes, y probables cambios genéticos y adaptativos de B. pertussis. En este documento se analizan las características, las ventajas y las desventajas de las vacunas de células enteras y de las vacunas acelulares. Se presentan las recomendaciones internacionales y se ofrece el posicionamiento de los participantes con respecto a la influencia del uso de vacunas acelulares y las desventajas potenciales de volver a utilizar vacunas de células enteras, en especial por su reactogenicidad. Por último, se analizan las estrategias para lograr un mejor control de la tos ferina en México.

Abstract Pertussis is a highly contagious disease caused by Bordetella pertussis, which may be preventable by vaccination. There are two types of vaccines: whole-cell vaccines and acellular vaccines. Since pertussis control worldwide is heterogeneous, re-emergence of whooping cough has been observed in some countries. This re-emergence has been related to several factors: increased susceptibility to infection, better detection of disease, problems in obtaining adequate vaccination coverage, increase in susceptible subjects (mainly under 6 months of age), loss of immunity in adolescents and young adults, and likely genetic and adaptive B. pertussis changes. This paper discusses whole-cell and acellular vaccines' characteristics, advantages, and disadvantages. International recommendations are presented, and the participants' position is offered regarding the influence of the use of acellular vaccines and the potential disadvantages of reintroducing whole-cell vaccines, mainly due to their reactogenicity. Finally, strategies to achieve better control of pertussis in Mexico are discussed.

Emerging Roles of Extracellular Vesicles in Pneumococcal Infections: Immunomodulators to Potential Novel Vaccine Candidates.

The Gram-positive bacterial pathogen, Streptococcus pneumoniae is a major global health threat that kills over one million people worldwide. The pneumococcus commonly colonizes the nasopharynx asymptomatically as a commensal, but is also capable of causing a wide range of life-threatening diseases such as pneumonia, meningitis and septicemia upon migration into the lower respiratory tract and spread to internal organs. Emergence of antibiotic resistant strains and non-vaccine serotypes has led to the classification of pneumococcal bacteria as a priority pathogen by the World Health Organization that needs urgent research into bacterial pathogenesis and development of novel vaccine strategies. Extracellular vesicles are spherical membrane bound structures that are released by both pathogen and host cells, and influence bacterial pathogenesis as well as the immune response. Recent studies have found that while bacterial vesicles shuttle virulence factors and toxins into host cells and regulate inflammatory responses, vesicles released from the infected host cells contain both bacterial and host proteins that are antigenic and immunomodulatory. Bacterial membrane vesicles have great potential to be developed as cell-free vaccine candidates in the future due to their immunogenicity and biostability. Host-derived vesicles isolated from patient biofluids such as blood and bronchoalveolar lavage could be used to identify potential diagnostic biomarkers as well as engineered to deliver desired payloads to specific target cells for immunotherapy. In this review, we summarize the recent developments on the role of bacterial and host vesicles in pneumococcal infections and future prospects in developing novel therapeutics and diagnostics for control of invasive pneumococcal diseases.

Development of a Bacterial Nanoparticle Vaccine Against Escherichia coli.

Currently, different subunit-based vaccine strategies against enterobacteria are being investigated. Among those, bacterial outer membrane vesicles (OMV) are promising candidates because of their immunogenic properties and safety. In order to develop an effective vaccine against this kind of pathogens, it is important to induce both systemic and mucosal immunity. For that reason, the oral route of administration would be an adequate option; although it still represents a challenge due to the particular and harsh conditions of the gut. To overcome these inconveniences, different strategies have been proposed, including the use of polymeric nanoparticles based on the copolymer between methyl vinyl ether and maleic anhydride (Gantrez AN). In the present work, a simple procedure for the preparation of heat-induced OMV (named as HT) obtained from Enterotoxigenic Escherichia coli (ETEC) loaded into these poly(anhydride) nanoparticles is described.

Mucosal Immunization Against Pertussis: Lessons From the Past and Perspectives.

Background: Current vaccination strategies against pertussis are sub-optimal. Optimal protection against Bordetella pertussis, the causative agent of pertussis, likely requires mucosal immunity. Current pertussis vaccines consist of inactivated whole B. pertussis cells or purified antigens thereof, combined with diphtheria and tetanus toxoids. Although they are highly protective against severe pertussis disease, they fail to elicit mucosal immunity. Compared to natural infection, immune responses following immunization are short-lived and fail to prevent bacterial colonization of the upper respiratory tract. To overcome these shortcomings, efforts have been made for decades, and continue to be made, toward the development of mucosal vaccines against pertussis. Objectives: In this review we systematically analyzed published literature on protection conferred by mucosal immunization against pertussis. Immune responses mounted by these vaccines are summarized. Method: The PubMed Library database was searched for published studies on mucosal pertussis vaccines. Eligibility criteria included mucosal administration and the evaluation of at least one outcome related to efficacy, immunogenicity and safety. Results: While over 349 publications were identified by the search, only 63 studies met the eligibility criteria. All eligible studies are included here. Initial attempts of mucosal whole-cell vaccine administration in humans provided promising results, but were not followed up. More recently, diverse vaccination strategies have been tested, including non-replicating and replicating vaccine candidates given by three different mucosal routes: orally, nasally or rectally. Several adjuvants and particulate formulations were tested to enhance the efficacy of non-replicating vaccines administered mucosally. Most novel vaccine candidates were only tested in animal models, mainly mice. Only one novel mucosal vaccine candidate was tested in baboons and in human trials. Conclusion: Three vaccination strategies drew our attention, as they provided protective and durable immunity in the respiratory tract, including the upper respiratory tract: acellular vaccines adjuvanted with lipopeptide LP1569 and c-di-GMP, outer membrane vesicles and the live attenuated BPZE1 vaccine. Among all experimental vaccines, BPZE1 is the only one that has advanced into clinical development.

The Path to New Pediatric Vaccines against Pertussis.

Whooping cough, or pertussis, mostly caused by Bordetella pertussis, is a respiratory disease that affects all age groups, but severe and fatal pertussis occurs almost exclusively in young children. The widespread use of whole-cell and, more recently, of acellular vaccines has substantially reduced the disease incidence. However, it has not been eliminated in any part of the world and has made a worrisome rebound in several areas. Cocoon and maternal immunization have been implemented in several countries but have their intrinsic limitations. To effectively control pertussis, novel vaccines are needed that protect against disease and prevent B. pertussis infection and transmission, which is not the case for current vaccines. Several approaches are contemplated, including alternative administration routes, such as nasal immunization, improvement of acellular vaccines by adding more antigens and T-cell-promoting adjuvants, and the development of novel vaccines, such as outer membrane vesicles and live attenuated vaccines. Among them, only a live attenuated vaccine has so far been assessed for safety and immunogenicity in preclinical models other than mice and is in clinical development. Before any of these vaccines can be used in neonates, extensive safety and immunogenicity assessment in pre-clinical neonatal models and in carefully designed clinical trials is necessary. The aim of this review is to discuss the current pertussis problem, implemented strategies to resolve it, the value of animal models and novel vaccine approaches.

Is there a potential for novel, nasal pertussis vaccines?

INTRODUCTION: Pertussis, caused by Bordetella pertussis, remains a major public health problem, despite high vaccination coverage. Furthermore, the disease incidence has increased recently, especially in countries that have switched from whole-cell to acellular pertussis vaccines. AREAS COVERED: Here, we provide a state-of-the art summary of the reasons for the pertussis resurgence and discuss potential solutions using current vaccines and challenges for the development of novel vaccines. PubMed was searched for publications with the terms pertussis and vaccines. Many new vaccine candidates are proposed but most have not reached clinical development. Most of them induce strong systemic immune responses and protection in mice. However, since B. pertussis is a mucosal pathogen, albeit with systemic effects, local immunity may be crucial to prevent B. pertussis infection and transmission. Recent efforts have focused on vaccine candidates able to induce immunity in the nasal cavity, and one of them is currently in clinical development. EXPERT COMMENTARY: New pertussis vaccines are needed to durably control the disease and circulation of B. pertussis. A major challenge is to prove efficacy against disease in randomized controlled trials, while it is feasible to provide evidence for prevention of infection, since asymptomatic carriage of B. pertussis is wide spread.

Isolate-Based Surveillance of Bordetella pertussis, Austria, 2018-2020.

Pertussis is a vaccine-preventable disease, and its recent resurgence might be attributable to the emergence of strains that differ genetically from the vaccine strain. We describe a novel pertussis isolate-based surveillance system and a core genome multilocus sequence typing scheme to assess Bordetella pertussis genetic variability and investigate the increased incidence of pertussis in Austria. During 2018-2020, we obtained 123 B. pertussis isolates and typed them with the new scheme (2,983 targets and preliminary cluster threshold of <6 alleles). B. pertussis isolates in Austria differed genetically from the vaccine strain, both in their core genomes and in their vaccine antigen genes; 31.7% of the isolates were pertactin-deficient. We detected 8 clusters, 1 of them with pertactin-deficient isolates and possibly part of a local outbreak. National expansion of the isolate-based surveillance system is needed to implement pertussis-control strategies.

Comparative proteomic analysis of outer membrane vesicles from Brucella suis, Brucella ovis, Brucella canis and Brucella neotomae.

Gram-negative bacteria release nanovesicles, called outer membrane vesicles (OMVs), from their outer membrane. Proteomics has been used to determine their composition. OMVs contain proteins able to elicit an immune response, so they have been proposed as a model to develop acellular vaccines. In this study, OMVs of Brucella suis, B. ovis, B. canis, and B. neotomae were purified and analyzed by SDS-PAGE, transmission electron microscopy and liquid chromatography coupled to mass spectrometry to determine the pan-proteome of these vesicles. In addition, antigenic proteins were detected by western blot with anti-Brucella sera. The in silico analysis of the pan-proteome revealed many homologous proteins, such as Omp16, Omp25, Omp31, SodC, Omp2a, and BhuA. Proteins contained in the vesicles from different Brucella species were detected by anti-Brucella sera. The occurrence of previously described immunogenic proteins derived from OMVs supports the use of these vesicles as candidates to be evaluated as an acellular brucellosis vaccine.

Will we have new pertussis vaccines?

Despite wide vaccination coverage with efficacious vaccines, pertussis is still not under control in any country. Two types of vaccines are available for the primary vaccination series, diphtheria/tetanus/whole-cell pertussis and diphtheria/tetanus/acellular pertussis vaccines, in addition to reduced antigen content vaccines recommended for booster vaccination. Using these vaccines, several strategies are being explored to counter the current pertussis problems, including repeated vaccination, cocoon vaccination and maternal immunization. With the exception of the latter, none have proven their effectiveness, and even maternal vaccination is not expected to ultimately control pertussis. Therefore, new pertussis vaccines are needed, and several candidates are in early pre-clinical development. They include whole-cell vaccines with low endotoxin content, outer membrane vesicles, new formulations, acellular vaccines with new adjuvants or additional antigens and live attenuated vaccines. The most advanced is the live attenuated nasal vaccine BPZE1. It provides strong protection in mice and non-human primates, is safe, even in immune compromised animals, and genetically stable after in vitro and in vivo passages. It also has interesting immunoregulatory properties without being immunosuppressive. It has successfully completed a first-in-man clinical trial, where it was found to be safe, able to transiently colonize the human respiratory tract and to induce immune responses in the colonized subjects. It is now undergoing further clinical development. As it is designed to reduce carriage and transmission of Bordetella pertussis, it may hopefully contribute to the ultimate control of pertussis.

Purificación del toxoide pertúsico de Bordetella pertussis / Pertussis Toxoid Purification of Bordetella pertussis

Introducción: el toxoide pertúsico es una proteína muy utilizada en las vacunas acelulares contra la tosferina. Desarrollar un protocolo para su purificación con pocos pasos y con parámetros de purificación adecuados, es muy importante para su caracterización química y la valoración de los efectos adversos que puede provocar al inocular principalmente a ratones. Los protocolos de purificación descritos en la literatura científica involucran varios pasos de purificación y bajos rendimientos. Objetivo: desarrollar un protocolo de purificación del toxoide pertúsico que garantice un grado de pureza alto y un rendimiento de más de 80% a partir de cultivos de un mutante de B. pertussis obtenido en el Centro Nacional de Investigaciones Científicas (CNIC). Métodos: para purificar el toxoide se usó una columna de intercambio catiónico Fractogel EMD SO-3 y se eluyó incrementando el pH y la concentración salina por pasos hasta obtener los resultados esperados. La determinación de proteínas totales se realizó mediante el micrométodo linealizado de Bradfor10 usando como patrón albúmina de suero bovina (BSA). Resultados: se obtuvo 3,28 mg de toxoide por cada litro de cultivo con un rendimiento de 86,7% y un grado de pureza de 96,7%. Conclusiones: el procedimiento de purificación descrito permite obtener el toxoide pertúsico con un rendimiento mayor que el 80% y alto grado de pureza, lo que garantiza la calidad requerida para su caracterización bioquímica e inmunológica.

Introduction: pertussis toxoid is a widely used in acellular vaccines against pertussis protein. Develop a protocol for purification with few steps and with parameters suitable purification is very important for chemical characterization and assessment of adverse effects that can lead to inoculate mainly mice. Purification protocols described in scientific literature involve several purification steps and low yields. Objective: to develop a protocol for purification of pertussis toxoid to ensure a high degree of purity and a yield of over 80% from cultures of a mutant of B. pertussis obtained at the National Center for Scientific Research (CNIC). Methods: for purifying the toxoid cation a Fractogel EMD SO-3 cationic interchange column was used by increasing the pH and salt concentration to obtain the expected results. The total protein determination was performed using linearized macromethod of Bradfor10 using as bovine serum albumin standard (BSA). Results: 3.28 mg toxoid was obtained per liter of culture with a yield higher than 86.7% and a purity of 96.7%. Conclusions: the purification process described allows for the pertussis toxoid with a higher yield than 80% and high purity, ensuring the quality required for biochemical and immunological characterization.

Pertussis: Where did we go wrong and what can we do about it?

Pertussis or whooping cough, mainly caused by the Gram-negative coccobacillus Bordetella pertussis, is a severe respiratory disease that can by life-threatening especially in young infants. It has recently made a spectacular come-back in high vaccination-coverage countries, such as the US, Australia and many European countries. Although a trend towards increased pertussis incidence was already visible before the switch from whole-cell to acellular vaccines, it was really since the introduction of the acellular vaccines that the number of cases reached record highs. Several hypotheses have been proposed to explain these observations. Unexpectedly fast waning of acellular vaccine-induced protection may be one of the major reasons. Furthermore, evidence from a recent non-human primate model suggests that acellular vaccines, although protective against pertussis disease, do not protect against B. pertussis infection, which may explain many of the current observations on the resurgence of pertussis. Optimized use of current vaccines has been explored, including cocoon vaccination of persons in close contact with newborn infants, neonatal vaccination and maternal immunization during pregnancy. All have their inherent limitations. New vaccines are therefore desperately needed, and current efforts have been geared towards the identification of novel antigens and adjuvants to prolong immunity and ameliorate protection. The most advanced vaccine candidate is live attenuated nasal BPZE1, a genetically modified B. pertussis derivative that has recently completed a first-in-man phase I trial and was shown to be safe in young male volunteers, able to transiently colonize the naso-pharynx and to induce antibody responses to B. pertussis antigens. This vaccine candidate is designed to protect against both pertussis disease and B. pertussis infection and may therefore be useful for long-term control of pertussis.

Live pertussis vaccines: will they protect against carriage and spread of pertussis?

Pertussis is a severe respiratory disease that can be fatal in young infants. Its main aetiological agent is the Gram-negative micro-organism Bordetella pertussis. Vaccines against the disease have been in use since the 1950s, and global vaccination coverage has now reached more than 85%. Nevertheless, the disease has not been controlled in any country, and has even made a spectacular come-back in the industrialized world, where the first-generation whole-cell vaccines have been replaced by the more recent, less reactogenic, acellular vaccines. Several hypotheses have been proposed to explain these observations, including the fast waning of acellular vaccine-induced protection. However, recent mathematical modelling studies have indicated that asymptomatic transmission of B. pertussis may be the main reason for the current resurgence of pertussis. Recent studies in non-human primates have shown that neither whole-cell, nor acellular vaccines prevent infection and transmission of B. pertussis, in contrast to prior exposure. New vaccines that can be applied nasally to mimic natural infection without causing disease may therefore be useful for long-term control of pertussis. Several vaccine candidates have been proposed, the most advanced of which is the genetically attenuated B. pertussis strain BPZE1. This vaccine candidate has successfully completed a first-in-man phase I trial and was shown to be safe in young male volunteers, able to transiently colonize the nasopharynx and to induce antibody responses to B. pertussis antigens in all colonized individuals. Whether BPZE1 will indeed be useful to ultimately control pertussis obviously needs to be assessed by carefully conducted human efficacy trials.

[Acellular vaccines (DTPa/dTpa) against whooping cough, protection duration]. / Vacunas acelulares (DTPa/dTpa) contra la tos ferina: duración de la protección.

INTRODUCTION: An increase in whooping cough in most of the developed countries has been detected in the last decade. OBJECTIVE: To determine whether the administration of dTpa vaccine instead of DTPa fifth dose is contributing to the appearance of these cases. METHODS: A descriptive study based on cases of whooping cough reported during an epidemic period in the city of Alicante in the first 5 months of 2014. Only pertussis cases confirmed by PCR were included in the study, and only those vaccinated with 5 doses were included in the analysis of the period of protection. RESULTS: A total of 104 cases of pertussis confirmed by PCR were reported, with 85 cases (82%) having had 5 doses of vaccine. The mean time and standard deviation (SD) of protection was 2.1±1.1 years with dTpa, and 5.1±1.5 years with DTPa (p<.001). In the protection, adjusted for age, it was observed that, after 3 years, only 47.6% of people vaccinated with dTpa were still protected, while people vaccinated with DTPa were 100% protected (P<.001). CONCLUSIONS: This study found that people who were properly vaccinated against pertussis and received their last re-vaccination dose with dTpa had a shorter period of protection than those who were vaccinated with DTPa.

Changing from whole-cell to acellular pertussis vaccines would trade superior tolerability for inferior protection.

Notifications of infant deaths, assumed to be related to the introduction of new pentavalent DTwP-Hib-HBV childhood vaccines, caused, during 2008-2010 in few Asian countries, temporary interruptions of the respective vaccination programs. The sudden appearance of fatal cases was due to increased awareness/publicity and improved safety monitoring/reporting in countries with relatively high background infant mortalities. WHO investigations could not establish any causal relationships and vaccinations were again resumed. Recently, questions were raised in one concerned country as to why not to change to less reactogenic acellular pertussis (aP)-containing vaccines that are available in private practice and are generally perceived as 'better'. For resource-poor countries, the financial impacts render such a switch impossible and would also not be supported by external funding. Furthermore, it would be a disservice to the children, as in recent years evidence of inferior long-term efficacy of aP vaccines has accumulated. This report summarizes current knowledge on comparative whole-cell pertussis (wP) and aP vaccine performance, outlines the new July 2014 WHO guidance on the choice of pertussis vaccines and presents recent data on outbreak protection, antibody waning, long-term protection, wP-priming, pathogen adaptation, transmission and herd immunity.

Whooping cough, twenty years from acellular vaccines introduction.

Clinical pertussis resulting from infection with B. pertussis is a significant medical and public health problem, despite the huge success of vaccination that has greatly reduced its incidence. The whole cell vaccine had an undeniable success over the last 50 years, but its acceptance was strongly inhibited by fear, only partially justified, of severe side effects, but also, in the Western world, by the difficulty to enter in combination with other vaccines: today multi-vaccine formulations are essential to maintain a high vaccination coverage. The advent of acellular vaccines was greeted with enthusiasm by the public health world: in the Nineties, several controlled vaccine trials were carried out: they demonstrated a high safety and good efficacy of new vaccines. In fact, in the Western world, the acellular vaccines completely replaced the whole cells ones. In the last years, ample evidence on the variety of protection of these vaccines linked to the presence of different antigens of Bordetella pertussis was collected. It also became clear that the protection provided, on average around 80%, leaves every year a significant cohort of vaccinated susceptible even in countries with a vaccination coverage of 95%, such as Italy. Finally, it was shown that, as for the pertussis disease, protection decreases over time, to leave a proportion of adolescents and adults unprotected. Waiting for improved pertussis vaccines, the disease control today requires a different strategy that includes a booster at 5 years for infants, but also boosters for teenagers and young adults, re-vaccination of health care personnel, and possibly of pregnant women and of those who are in contact with infants (cocooning). Finally, the quest for better vaccines inevitably tends towards pertussis acellular vaccines with at least three components, which have demonstrated superior effectiveness and have been largely in use in Italy for fifteen years.

Acellular pertussis vaccine based on outer membrane vesicles capable of conferring both long-lasting immunity and protection against different strain genotypes.

Despite high vaccination coverage rates, pertussis continues to be a global concern, with increased incidence widely noted. The current pertussis epidemiologic situation has been mainly attributed to waning immunity and pathogen adaptation. To improve the disease control, a new generation of vaccines capable to overcome those weaknesses associated to the current vaccines need to be developed. Previously we have demonstrated that the outer membrane vesicles obtained from the recombinant Bordetella pertussis strain expressing PagL enzyme (OMVs(BpPagL)) are good vaccine candidates to protect against pertussis. In this work the OMVs(BpPagL) formulated with diphtheria and tetanus toxoids (Tdap(OMVsBpPagL)) was used to evaluate its capacity to offer protection against Argentinean clinical isolates and to induce long-term immunity. To these aims BALB/c mice were immunized with Tdap(OMVsBpPagL) and challenged with sublethal doses of the clinical isolate Bp106 selected as a representative circulating isolate. Comparisons with a current commercial Tdap vaccine used at a dose in which pertussis toxin level was equivalent to that of Tdap(OMVsBpPagL) were performed. With the normalized doses of both vaccines we observed that Tdap(OMVsBpPagL) protected against the clinical isolate infection, whereas current commercial Tdap vaccine showed little protection against such pathogen. Regarding long-term immunity we observed that the Tdap(OMVsBpPagL) protective capacity against the recommended WHO reference strain persisted at least 9 months. In agreement with these results Tdap(OMVsBpPagL) induced Th1 and Th2 immune response. In contrast, commercial Tdap induced Th2 but weak Th1 responses. All results presented here showed that Tdap(OMVsBpPagL) is an interesting formulation to be considered for the development of novel acellular multi-antigen vaccine.

Virulence of pertactin-negative Bordetella pertussis isolates from infants, France.

Bordetella pertussis isolates that do not express pertactin (PRN) are increasing in regions where acellular pertussis vaccines have been used for >7 years. We analyzed data from France and compared clinical symptoms among infants <6 months old infected by PRN-positive or PRN-negative isolates. No major clinical differences were found between the 2 groups.