Boosting Teenagers With Acellular Pertussis Vaccines Containing Recombinant or Chemically Inactivated Pertussis Toxin: A Randomized Clinical Trial.

BACKGROUND: Protection induced by acellular pertussis (aP) vaccines is partial and short-lived, especially in teenagers, calling for novel immunization strategies. METHODS: We conducted an investigator-driven proof-of-concept randomized controlled trial in aP-primed adolescents in Geneva to assess the immunogenicity and reactogenicity of a novel recombinant aP (r-aP) vaccine including recombinant pertussis toxin (PT) and filamentous hemagglutinin (FHA) coadministered with tetanus-diphtheria toxoids (Td), compared to a licensed tetanus-diphtheria-aP vaccine containing chemically detoxified PT (cd/Tdap). The primary immunological endpoints were day 28/365 geometric mean concentrations (GMCs) of total and neutralizing anti-PT antibodies. Memory B cells were assessed. RESULTS: Sixty-two aP-primed adolescents were randomized and vaccinated with r-aP + Td or cd/Tdap. Reactogenicity, adverse events, and baseline GMCs were similar between the groups. Day 28 PT-neutralizing GMCs were low after cd/Tdap (73.91 [95% confidence interval {CI}, 49.88-109.52] IU/mL) and approximately 2-fold higher after r-aP + Td (127.68 [95% CI, 96.73-168.53] IU/mL; P = .0162). Anti-PT GMCs were also low after cd/Tdap (52.43 [95% CI, 36.41-75.50] IU/mL) and 2-fold higher after r-aP + Td (113.74 [95% CI, 88.31-146.50] IU/mL; P = .0006). Day 28 anti-FHA GMCs were similar in both groups. Day 365 anti-PT (but not PT-neutralizing) GMCs remained higher in r-aP + Td vaccinees. PT-specific memory B cells increased significantly after r-aP + Td but not cd/Tdap boosting. CONCLUSIONS: Boosting aP-primed adolescents with r-aP induced higher anti-PT and PT-neutralizing responses than cd/Tdap and increased PT-specific memory B cells. Despite this superior immunogenicity, r-aP may have to be given repeatedly, earlier, and/or with novel adjuvants to exert an optimal influence in aP-primed subjects. CLINICAL TRIALS REGISTRATION: NCT02946190.

Tumor exosomes: a double-edged sword in cancer therapy.

Tumor cells produce and secrete more nucleic acids, proteins and lipids than normal cells. These molecules are transported in the blood or around the cells in membrane-encapsulated exosomes. Tumor-derived or tumor-associated exosomes (usually 30-100 nm in diameter) contain abundant biological contents resembling those of the parent cells along with signaling messengers for intercellular communication involved in the pathogenesis, development, progression, and metastasis of cancer. As these exosomes can be detected and isolated from various body fluids, they have become attractive new biomarkers for the diagnosis and prognosis of cancer. Furthermore, tumor exosomes have also attracted increasing attention due to their potential as novel therapeutic strategies for the treatment of cancers. On the one hand, the lipid bilayer membrane-encapsulated vesicles are promising carriers of drugs and other therapeutic materials targeting specific cancer cells. On the other hand, tumor exosomes are important mediators for modulation of the microenvironment that orchestrates events critical to the growth and metastasis of cancer cells as well as chemoresistance. Here, we summarize the advances in our understanding of tumor-associated or tumor-derived exosomes in recent years, and discuss their roles in cancer development, progression, invasion, and metastasis of cancers and, more importantly, their potential in strategies for precision therapy of various cancers as well as important caveats.

A recombinant iron transport protein from Bordetella pertussis confers protection against Bordetella parapertussis.

Whooping cough, which is caused by Bordetella pertussis and B. parapertussis, is a reemerging disease. New protective antigens are needed to improve the efficacy of current vaccines against both species. Using proteomic tools, it was here found that B. parapertussis expresses a homolog of AfuA, a previously reported new vaccine candidate against B. pertussis. It was found that this homolog, named AfuABpp , is expressed during B. parapertussis infection, exposed on the surface of the bacteria and recognized by specific antibodies induced by the recombinant AfuA cloned from B. pertussis (rAfuA). Importantly, the presence of the O-antigen, a molecule that has been found to shield surface antigens on B. parapertussis, showed no influence on antibody recognition of AfuABpp on the bacterial surface. The present study further showed that antibodies induced by immunization with the recombinant protein were able to opsonize B. parapertussis and promote bacterial uptake by neutrophils. Finally, it was shown that this antigen confers protection against B. parapertussis infection in a mouse model. Altogether, these results indicate that AfuA is a good vaccine candidate for acellular vaccines protective against both causative agents of whooping cough.

The Need to Optimize Adolescent Immunization.

The adolescent period heralds the pediatric patient's transition into adulthood. It is a time of dynamic development during which effective preventive care measures can promote safe behaviors and the development of lifelong health habits. One of the foundations of preventive adolescent health care is timely vaccination, and every visit can be viewed as an opportunity to update and complete an adolescent's immunizations.In the past decade, the adolescent immunization schedule has expanded to include 2 doses of quadrivalent meningococcal conjugate vaccine, 1 dose of tetanus, diphtheria, acellular pertussis, absorbed vaccine, 2 or 3 doses of human papillomavirus vaccine, depending on the child's age, and an annual influenza vaccine. In addition, during adolescent visits, health care providers can determine whether catch-up vaccination is needed to meet early childhood recommendations for hepatitis B; hepatitis A; measles, mumps, rubella; poliovirus; and varicella vaccines. New serogroup B meningococcal vaccines are now available for those at increased risk for meningococcal disease; in addition, these serogroup B meningococcal vaccines received a Category B recommendation for healthy adolescents, where individual counseling and risk-benefit evaluation based on health care provider judgements and patient preferences are indicated. This clinical report focuses on the epidemiology of adolescent vaccine-preventable diseases by reviewing the rationale for the annual universally recommended adolescent immunization schedule of the American Academy of Pediatrics, the American Academy of Family Physicians, the Centers for Disease Control and Prevention, and the American Congress of Obstetricians and Gynecologists. In addition, the barriers that negatively influence adherence to this current adolescent immunization schedule will be highlighted.

Reporter cell lines for detection of pertussis toxin in acellular pertussis vaccines as a functional animal-free alternative to the in vivo histamine sensitization test.

Detoxified pertussis toxin (pertussis toxoid) is a major antigen in acellular pertussis vaccines. Testing these vaccines on the presence of residual pertussis toxin (PTx) and reversion to toxicity is performed by the regulatory required in vivo Histamine Sensitization test (HIST). Lack of mechanistic understanding of the HIST, technical handicaps and animal welfare concerns, have promoted the development of alternative methods. As the majority of the cellular effects of PTx depend on its ability to activate intracellular pathways involving cAMP, the in vitro cAMP-PTx assay was developed. Although this assay could be used to detect PTx activity, it lacked sensitivity and robustness for use in a quality control setting. In the present study, novel reporter cell lines (CHO-CRE and A10-CRE) were generated that stably express a reporter construct responsive to changes in intracellular cAMP levels. These reporter cell lines were able to detect PTx in a concentration-dependent manner when combined with fixed amounts of forskolin. The CHO-CRE cell line enabled detection of PTx in the context of a multivalent vaccine containing aP, with a sensitivity equal to the HIST. However, the sensitivity of the A10-CRE cells was insufficient for this purpose. The experiments also suggest that the CHO-CRE reporter cell line might be suitable for assessment of cellular effects of PTd reverted to PTx. The CHO-CRE reporter cell line provides a platform that meets the criteria for specificity and sensitivity and is a promising in vitro model with potential to replace the HIST.

A novel high-throughput assay to quantify the vaccine-induced inhibition of Bordetella pertussis adhesion to airway epithelia.

BACKGROUND: Pertussis or whooping cough is an acute respiratory illness caused by the Gram-negative pathogen Bordetella pertussis. Despite high vaccination coverage whooping cough is currently re-emerging in many developed countries. Although the causes of pertussis resurgence are matter of debate, emerging evidences suggest that acellular vaccines efficiently protect against the hallmark symptoms of pertussis disease but fail to prevent colonization. This presumably impacts on increased risk of bacterial transmission and consequent spread throughout the population. These evidences suggest that improved vaccines may be required for efficient bacterial clearance in the upper respiratory tract. Consequently, there is a need for novel bioassays to evaluate at pre-clinical or clinical level the impact of different vaccines on B. pertussis colonization. RESULTS: We developed a high-throughput bacterial adhesion inhibition (BAI) assay based on human respiratory cell lines and on live bacteria chemically conjugated to a fluorescent dye. Employing A549 cells as model, we evaluated the impact of antibodies elicited by acellular (aP) and whole cell (wP) vaccines on B. pertussis adhesion in vitro. Moreover, we settled the method also on polarized Calu-3 cells grown at air-liquid interface (ALI), showing that this assay can be extended to more complex cell models mimicking the airway epithelium. CONCLUSIONS: We proved that this method is a sensitive, rapid and reproducible system to evaluate the anti-adhesive properties of vaccine-induced antibodies and can be employed to assess improved pertussis vaccines.

Characterization of the immune response induced by pertussis OMVs-based vaccine.

For the development of a third generation of pertussis vaccine that could improve the control of the disease, it was proposed that the immune responses induced by the classic whole cell vaccine (wP) or after infection should be used as a reference point. We have recently identified a vaccine candidate based on outer membrane vesicles (OMVs) derived from the disease etiologic agent that have been shown to be safe and protective in mice model of infection. Here we characterized OMVs-mediated immunity and the safety of our new candidate. We also deepen the knowledge of the induced humoral response contribution in pertussis protection. Regarding the safety of the OMVs based vaccine (TdapOMVsBp,) the in vitro whole blood human assay here performed, showed that the low toxicity of OMVs-based vaccine previously detected in mice could be extended to human samples. Stimulation of splenocytes from immunized mice evidenced the presence of IFN-γ and IL-17-producing cells, indicated that OMVs induces both Th1 and Th17 response. Interestingly TdapOMVsBp-raised antibodies such as those induced by wP and commercial acellular vaccines (aP) which contribute to induce protection against Bordetella pertussis infection. As occurs with wP-induced antibodies, the TdapOMVsBp-induced serum antibodies efficiently opsonized B. pertussis. All the data here obtained shows that OMVs based vaccine is able to induce Th1/Th17 and Th2 mixed profile with robust humoral response involved in protection, positioning this candidate among the different possibilities to constitute the third generation of anti-pertussis vaccines.

Vacunas anti-pertussis: acelular versus celular. ¿Acaso un regreso al pasado? / Pertussis vaccines: acellular versus whole cell. Perhaps a return to the past?

The resurgence of pertussis in the world and in our country has questioned the effectiveness of cellular and acellular vaccines. The reason why pertussis has not been controlled or eliminated after 70 years of implementation of the vaccination is probably multifactorial. This article, on the basis of questions and answers, describes the benefits and limitations of both cellular and acellular vaccines and suggests new strategies of vaccination in childhood. It is a fact that the currently applied vaccination does not eliminate the circulation of Bordetella pertussis in the community. Perhaps the introduction of vaccines with live B. pertussis, inhalation, will be able to eliminate the disease around the world.

El resurgimiento de la coqueluche en el mundo y en nuestro país ha puesto en tela de juicio la eficacia de las vacunas celulares y acelulares. Las razones de por qué la coqueluche no es controlada ni eliminada después de 70 años de implementación de la vacunación son diversas y probablemente multifactoriales. En este artículo, en base a preguntas y respuestas, se describen las bondades y limitaciones de tanto vacunas celulares como acelulares y queda sugerida una mejor forma de administrar ambas en la infancia. Es un hecho que la vacunación actualmente aplicada no elimina la circulación de Bordetella pertussis en la comunidad. Tal vez la introducción de vacunas con B. pertussis viva, inhalatoria, sea capaz de eliminar la enfermedad de la humanidad.

Identification of pertussis-specific effector memory T cells in preschool children.

Whooping cough remains a problem despite vaccination, and worldwide resurgence of pertussis is evident. Since cellular immunity plays a role in long-term protection against pertussis, we studied pertussis-specific T-cell responses. Around the time of the preschool acellular pertussis (aP) booster dose at 4 years of age, T-cell memory responses were compared in children who were primed during infancy with either a whole-cell pertussis (wP) or an aP vaccine. Peripheral blood mononuclear cells (PBMCs) were isolated and stimulated with pertussis vaccine antigens for 5 days. T cells were characterized by flow-based analysis of carboxyfluorescein succinimidyl ester (CFSE) dilution and CD4, CD3, CD45RA, CCR7, gamma interferon (IFN-γ), and tumor necrosis factor alpha (TNF-α) expression. Before the aP preschool booster vaccination, both the proliferated pertussis toxin (PT)-specific CD4(+) and CD8(+) T-cell fractions (CFSE(dim)) were higher in aP- than in wP-primed children. Post-booster vaccination, more pertussis-specific CD4(+) effector memory cells (CD45RA(-) CCR7(-)) were induced in aP-primed children than in those primed with wP. The booster vaccination did not appear to significantly affect the T-cell memory subsets and functionality in aP-primed or wP-primed children. Although the percentages of Th1 cytokine-producing cells were alike in aP- and wP-primed children pre-booster vaccination, aP-primed children produced more Th1 cytokines due to higher numbers of proliferated pertussis-specific effector memory cells. At present, infant vaccinations with four aP vaccines in the first year of life result in pertussis-specific CD4(+) and CD8(+) effector memory T-cell responses that persist in children until 4 years of age and are higher than those in wP-primed children. The booster at 4 years of age is therefore questionable; this may be postponed to 6 years of age.

Increasing provision of adolescent vaccines in primary care: a randomized controlled trial.

OBJECTIVES: To assess the effectiveness of in-person and webinar-delivered AFIX (Assessment, Feedback, Incentives, and eXchange) consultations for increasing adolescent vaccine coverage. METHODS: We randomly assigned 91 primary care clinics in North Carolina, serving 107 443 adolescents, to receive no consultation or an in-person or webinar AFIX consultation. We delivered in-person consultations in April through May 2011 and webinar consultations in May through August 2011. The state's immunization registry provided vaccine coverage data for younger patients (ages 11-12 years) and older patients (ages 13-18 years) for 3 adolescent vaccines: tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap); meningococcal; and human papillomavirus (HPV) vaccines (≥1 dose, females only). RESULTS: At the 5-month follow-up, AFIX consultations increased vaccine coverage among younger adolescents. Patients in the in-person arm experienced coverage changes that exceeded those in the control arm for Tdap (3.4% [95% confidence interval (CI): 2.2 to 4.6]), meningococcal (4.7% [95% CI: 2.3 to 7.2], and HPV (1.5% [95% CI: 0.3 to 2.7]) vaccines. Patients in the webinar versus control arm also experienced larger changes for these vaccines. AFIX did little to improve coverage among older adolescents. At 1 year, the 3 arms showed similar coverage changes. The effectiveness of in-person and webinar consultations was not statistically different at either time point (all, P >.05). CONCLUSIONS: Webinar AFIX consultations were as effective as in-person consultations in achieving short-term increases in vaccine coverage for younger adolescents. AFIX consultations for adolescents need improvement to have a stronger and more durable impact, especially for HPV vaccine.

A CpG-containing oligodeoxynucleotide adjuvant for acellular pertussis vaccine improves the protective response against Bordetella pertussis.

We investigated the adjuvant effect of CpG ODN alone or in combination with aluminum hydroxide on the immune response to the three main antigens presented in current acellular pertussis vaccines: pertussis toxoid, filamentous haemagglutinin and pertactin. The development of protection in mice was investigated for the intra-peritoneal and intra-nasal immunisation routes. The results showed that CpG ODN alone, or in combination with aluminum hydroxide, gave enhancement in anti-pertussis toxin, anti- filamentous haemagglutinin and especially anti-pertactin titers after mucosal immunisation. Higher macrophage NO levels indicating activation were found when the antigens were co-formulated with CpG ODN. Vaccines containing CpG ODN gave enhanced humoral and CMI responses with a shift toward Th-1 and increased protection against challenge infection with B.pertussis in mice.

Difteria-tétano-pertusis / Diphtheria-tetanus-pertussis

Los componentes de la vacuna contra la Difteria, Tétanos y Tosferina a células completas (DTP) fueron integrados a mediados de la década de los años 40 e igualmente, fue administrada en forma masiva, llevando virtualmente a la eliminación de la difteria. Posteriormente, a partir de 1991, el Toxoide Diftérico y el Tetánico se combinan con la vacuna acelular contra la tosferina, ya que no contiene células completas de B. pertussis, sino solo unas cuantas proteínas antigénicas (DTPa). En los últimos 10 años se ha observadoaumento de los casos de tosferina en niños mayores, adolescentes y adultos jóvenes. La presentación de tosferina a estas edades es atípica, de difícil diagnóstico, no son adecuadamente tratadas y conforman grupos que actúan como reservorios de la enfermedad, que favorecen la trasmisión de la B. pertussis a los niños de menor edad. Con la aprobación en 2005 de la vacuna dTpa, se puede completar el esquemade vacunación o administrar como dosis de refuerzo desde los 7 años de edad, a las embarazadas a partir de las 20 semanas de gestación y en el puerperio. Con esta estrategia se logrará la disminución en la aparición de nuevos casos de tosferina. Es bueno recordar que, ni la infección natural, ni la vacunación con un esquema completo, confieren inmunidad permanente

The components of whole cell vaccine against Diphtheria, Tetanus and Pertussis (DTP) were integrated during the mid years 40. The vaccine was also massively administered leading to the virtually elimination of diphteria. Later, after 1991 diphteric and tetanic toxoidswere combined with the acellular vaccine against pertussis, since it does not contain whole cells of B pertussis, but only some antigenic proteins (DTPa). During the last 10 years an increase in Pertussis cases has occured in elder children, adolescents and young adults. The clinical presentation of Pertussis at these ages is atypical, the disease is difficult to diagnose, patients are not treated adequately andtherefore constitute groups that act as reservoirs of the disease, and favor the transmission of B pertussis to small children. With the approval in 2005 of the vaccine dTpa, the vaccination scheme may be completed, or a booster dose may be administered from 7 yearsof age, or during pregnancy after 20 weeks of gestation or during puerperium. The appearance of new cases of pertussis may be avoidedwith this strategy. It should be remembered that, neither natural infection, nor the vaccination with a complete scheme, confers permanentimmunity

Antigen presentation on artificial acellular substrates: modular systems for flexible, adaptable immunotherapy.

BACKGROUND: Recent findings on T cells and dendritic cells have elucidated principles that can be used for a bottom-up approach to engineering artificial antigen presentation on synthetic substrates. OBJECTIVE/METHODS: To compare the latest artificial antigen-presenting cell (aAPC) technology, focussing on acellular systems because they offer advantages such as easy tunability and rapid point-of-care application compared with cellular systems. We review acellular aAPC performance and discuss their promise for clinical applications. RESULTS/CONCLUSION: Acellular aAPCs are a powerful alternative to natural-cell-based therapies, offering flexibility and modularity for incorporation oSf a variety of stimuli, hence increasing precision. Current technologies should adapt physiologically important signals within safe materials to more closely approximate their cellular counterparts. These constructs could be administered parenterally as APC replacements for active vaccines or used ex vivo for adoptive immunotherapy.

Improved efficacy of a licensed acellular pertussis vaccine, reformulated in an adjuvant emulsion of liposomes in oil, in a murine model.

The immunogenicities and efficacies of a licensed diphtheria, tetanus, acellular pertussis, and inactivated poliovirus vaccine and the same vaccine formulated in a liposome/oil emulsion adjuvant were compared in a mouse model of pertussis respiratory infection. A single dose of the liposome/oil emulsion-adjuvanted vaccine produced significantly higher antibody levels than one dose of the licensed vaccine and protected mice from Bordetella pertussis infection with an efficacy equivalent to that of three doses of the licensed vaccine.

Potent CTL induction by a whole cell pertussis vaccine in anti-tumor peptide immunotherapy.

Promising yet limited clinical responses have been reported for peptide based immunotherapy against tumors. In order to induce more potent cytolytic CD8 T cell responses, we investigated the use of Bordetella pertussis vaccine as an adjuvant for peptide immunization. A whole cell (Wc) vaccine has been known to induce a Th1 biased immune response while an acellular (Ac) vaccine tends to induce that of the Th2 type. Natural infection by B. pertussis helps to maintain a robust Th1 memory in the host population. To examine the adjuvant activity of the pertussis vaccine, we immunized mice with an ovalbumin peptide as a model tumor antigen, and monitored the development of anti-tumor activities. The addition of either the Ac or the Wc vaccine helped expand the specific CD8 T cells. However, there was a marked difference in the induced cytolytic activity where the Wc vaccine was superior to the Ac. The Wc vaccine was also more effective in inducing in vivo tumor rejection. The adjuvant activity was not only effective against ovalbumin, but was also evident when an endogenous tumor antigen, Wilms' tumor 1 gene product, was targeted. These results indicate that, although the Wc vaccine does not share the same antigen specificity with tumor cells, it can aid in the development of highly cytolytic CD8 T cells as an adjuvant at the site of peptide immunization.

Lipopolysaccharide analogs improve efficacy of acellular pertussis vaccine and reduce type I hypersensitivity in mice.

Pertussis is an infectious disease of the respiratory tract that is caused by the gram-negative bacterium Bordetella pertussis. Although acellular pertussis (aP) vaccines are safe, they are not fully effective and thus require improvement. In contrast to whole-cell pertussis (wP) vaccines, aP vaccines do not contain lipopolysaccharide (LPS). Monophosphoryl lipid A (MPL) and Neisseria meningitidis LpxL2 LPS have been shown to display immune-stimulating activity while exerting little endotoxin activity. Therefore, we evaluated whether these LPS analogs could increase the efficacy of the aP vaccine. Mice were vaccinated with diphtheria-tetanus-aP vaccine with aluminum, MPL, or LpxL2 LPS adjuvant before intranasal challenge with B. pertussis. Compared to vaccination with the aluminum adjuvant, vaccination with either LPS analog resulted in lower colonization and a higher pertussis toxin-specific serum immunoglobulin G level, indicating increased efficacy. Vaccination with either LPS analog resulted in reduced lung eosinophilia, reduced eosinophil numbers in the bronchoalveolar lavage fluid, and the ex vivo production of interleukin-4 (IL-4) by bronchial lymph node cells and IL-5 by spleen cells, suggesting reduced type I hypersensitivity. Vaccination with either LPS analog increased serum IL-6 levels, although these levels remained well below the level induced by wP, suggesting that supplementation with LPS analogs may induce some reactogenicity but reactogenicity considerably less than that induced by the wP vaccine. In conclusion, these results indicate that supplementation with LPS analogs forms a promising strategy that can be used to improve aP vaccines.

ADP-ribosylation activity in pertussis vaccines and its relationship to the in vivo histamine-sensitisation test.

Pertussis toxin (PTx) is a major virulence factor produced by Bordetella pertussis. In its detoxified form (PTd), it is an important component of acellular pertussis vaccines although some residual PTx activity may likely be present because of the limitations of the detoxification processes used. Furthermore, different detoxification procedures have been shown to result in different amino acid side-chain modifications for the resulting PTd. The histamine-sensitisation test (HIST) in mice is currently used for the safety testing of these vaccines. However, an alternative test is needed because of large assay variability and ethical concerns. The ADP-ribosylation enzyme activity of PTx is thought to be the major factor responsible for the histamine-sensitising activity detected in vivo. In the present study, the ADP-ribosylation activity in different acellular pertussis-based combination vaccine formulations was measured and compared with reactivity in the HIST. The results indicated that different products showed differences in ADP-ribosylation activity and a level which would be significant in relation to the reactivity seen in the HIST could not be defined, except for vaccines that contain genetically detoxified PTx, which do not have enzymatic activity nor in vivo toxicity. Different detoxification procedures as well as formulation factors could contribute to this variation. Relying solely on the residual enzyme activity of PTx in vaccines containing chemically detoxified PTd may not fully reflect the in vivo reactivity observed by the HIST. Refinement of the in vitro test to include a step which monitors the B-subunit activity of PTx may provide a better correlation with the in vivo HIST.

Revaccination of children after completion of standard chemotherapy for acute leukemia.

BACKGROUND: After the treatment of patients with acute leukemia, there is a decrease in vaccine-specific antibody and an increased susceptibility to certain vaccine-preventable diseases. A simple revaccination schedule is warranted. METHOD: Fifty-nine children (age, 1-18 years) who had completed standard chemotherapy in accordance with Medical Research Council of United Kingdom protocols were recruited. All children received a single dose of Haemophilus influenzae type b (Hib), tetanus, diphtheria, acellular pertussis, meningococcus C, polio, measles, mumps, and rubella vaccines > or = 6 months after completion of treatment. Antibody concentrations were measured before vaccination and 2-4 weeks and 12 months after vaccination. RESULTS: Prevaccination antibody levels were protective for all patients for tetanus (geometric mean concentration [GMC], 0.13 IU/mL; 95% CI, 0.1-0.17 IU/mL), for 87% for Hib (GMC, 0.5 microg/mL; 95% CI, 0.37-0.74 microg/mL), for 71% for measles (GMC, 301 mIU/mL; 95% CI, 163-557 mIU/mL), for 12% for meningococcus C (geometric mean titer [GMT], 1:2.9; 95% CI, 1:2.2 to 1:3.9), and for 11% for all 3 poliovirus serotypes. Revaccination resulted in a significant increase in levels of antibody to each vaccine antigen, with 100% of patients achieving optimal antitetanus antibody concentrations (defined as > 0.1 IU/mL; 1.5 IU/mL; 95% CI, 1.1-2.1 IU/mL), 93% achieving optimal antibody concentrations to Hib (defined as > 1.0 microg/mL; 6.5 microg/mL; 95% CI, 5.1-8.2 microg/mL), 94% achieving optimal antibody concentrations to measles (defined as > or = 120 mIU/mL; 2720 mIU/mL; 95% CI, 1423-5198 mIU/mL), 96% achieving optimal antibody concentrations to meningococcus C (defined as > or = 1:8; 1:1000; 95% CI, 1:483-1:2064), and 85% achieving optimal antibody concentrations to all the 3 poliovirus serotypes (defined as > or = 1:8). For the majority of subjects, protection persisted for at least 12 months after vaccination. CONCLUSION: Revaccination of children after standard chemotherapy is important, and protection can be achieved in the majority of these children using a simple schedule of 1 vaccine dose at 6 months after completion of leukemia therapy.

Lung pathology and immediate hypersensitivity in a mouse model after vaccination with pertussis vaccines and challenge with Bordetella pertussis.

While evaluating vaccine efficacy against clinical Bordetella pertussis isolates in mice, after challenge vaccinated mice showed increased lung pathology with eosinophilia, compared to challenged, non-vaccinated animals. This led us to study bacterial clearance, lung pathology, lung TNF-alpha expression, and parameters of immediate hypersensitivity (IH), being serum IgE levels, eosinophil numbers in the bronchoalveolar lavage fluid, and ex vivo IL-4, IL-5, IL-10, IL-13, and IFN-gamma production by the bronchial lymph node cells. BALB/c mice received a combined Diphtheria (D), Tetanus (T), Poliomyelitis, and whole-cell Pertussis vaccine (WCV), a combined D, T, and three-component acellular Pertussis vaccine (ACV), aluminium hydroxide adjuvant, or PBS, 28 and 14 days before B. pertussis infection. Similarly treated non-infected mice were taken as a control. Infection induced pathology; this induction was stronger after (especially WCV) vaccination. WCV but not ACV vaccination induced TNF-alpha expression after challenge. After challenge, IH parameters were strongly increased by (especially ACV) vaccination. Vaccinated IL-4 KO mice showed similar clearance and pathology, in the absence of IgE and with reduced numbers of eosinophils. Vaccinated (Th1-deficient) T-bet KO mice showed reduced clearance and similar pathology. In summary, after challenge vaccination increased lung pathology, TNF-alpha expression (only WCV), and IH parameters. Th1 cells were critical for clearance.