RESUMO
BACKGROUND: Schistosomiasis caused by Schistosoma mansoni (Sm) is a chronic, debilitating and potentially deadly neglected tropical disease. The licensure of a vaccine to prevent schistosomiasis would represent a major breakthrough in public health. METHODS: The safety and immunogenicity of a candidate Sm vaccine were assessed in this phase I, double-blind, dose-escalation trial. Seventy-two healthy Sm-naïve 18-50â¯year olds were randomized to receive 3 doses â¼â¯8â¯weeks apart of saline placebo, or 10⯵g, 30⯵g, or 100⯵g of recombinant Sm-Tetraspanin-2 vaccine formulated on aluminum hydroxide adjuvant (Sm-TSP-2/Al) with or without 5⯵g of glucopyranosyl lipid A aqueous formulation (GLA-AF). Clinical and serologic responses were assessed for 1â¯year after dose 3. RESULTS: Vaccines were safe and well-tolerated. The most common reactions were injection site tenderness and pain, and headache and fatigue. Tenderness and pain were more frequent in groups receiving vaccine with GLA-AF than placebo (pâ¯=â¯0.0036 and pâ¯=â¯0.0014, respectively). Injection site reactions among those given Sm-TSP-2/Al with GLA-AF lasted 1.22 and 1.33â¯days longer than those receiving Sm-TSP-2/Al without GLA-AF or placebo (pâ¯<â¯0.001 for both). Dose- and adjuvant-related increases in serum IgG against Sm-TSP-2 were observed. Peak IgG levels occurred 14â¯days after dose 3. Seroresponse frequencies were low among recipients of Sm-TSP-2/Al without GLA-AF, but higher among subjects receiving 30⯵g or 100⯵g of Sm-TSP-2/Al with GLA-AF. More seroresponses were observed among those given 30⯵g or 100⯵g of Sm-TSP-2/Al with GLA-AF compared to placebo (pâ¯=â¯0.023 and pâ¯<â¯0.001, respectively). Seroresponse frequencies were 0%, 30%, 50%, and 89%, respectively, among those given placebo, or 10⯵g, 30⯵g or 100⯵g of Sm-TSP-2/Al with GLA-AF, suggesting a dose-response relationship for Sm-TSP-2/Al with GLA-AF (pâ¯=â¯0.0001). CONCLUSIONS: Sm-TSP-2/Al with or without GLA-AF was safe and well tolerated in a Sm-naïve population. A vaccine like the one under development may represent our best hope to eliminating this neglected tropical disease.
Assuntos
Anticorpos Anti-Helmínticos/sangue , Glucosídeos/imunologia , Imunogenicidade da Vacina , Lipídeo A/imunologia , Esquistossomose/prevenção & controle , Vacinas/imunologia , Adjuvantes Imunológicos/administração & dosagem , Adolescente , Adulto , Animais , Antígenos de Helmintos/imunologia , Estudos de Coortes , Citocinas/imunologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Voluntários Saudáveis , Humanos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Schistosoma mansoni , Vacinas/efeitos adversos , Adulto JovemRESUMO
Recent studies have suggested that among those receiving seasonal influenza vaccine (SIV), reduced immunogenicity is observed in recently vaccinated (RV; within the past season or 2) persons when compared with those not recently vaccinated (NRV). We performed a meta-analysis to assess the effect of recent immunization with SIV on serum H5 hemagglutination inhibition (HAI) antibody responses after influenza A/H5N1 vaccination using data from a series of randomized controlled trials. The primary outcome was seroconversion measured by HAI assays following receipt of 2 doses of H5N1 vaccine. The geometric mean titer (GMT) of serum HAI antibody after vaccination was the secondary outcome. Analyses were performed using propensity score (PS) matching. The PS for each individual in the meta-analysis cohort was calculated using logistic regression and covariates included age, gender, race, antigen dose, adjuvant, statin use and vaccine manufacturer. 2015 subjects enrolled in 7 clinical trials were eligible for inclusion in the meta-analysis cohort; among these, 915 (45%) were RV. 901 RV subjects were matched (1:1) with replacement to a subject who was NRV. Subjects who received SIV within the previous season were significantly less likely to seroconvert following H5N1 vaccination (adjusted odds ratio 0.76; 95%CI 0.60-0.96; pâ¯=â¯0.024), and the GMT was 18% higher among NRV subjects (GM ratio of HAI antibody 1.18; 95%CI 1.04-1.33; pâ¯=â¯0.008). Further work is needed to better define the effects of, and mechanisms contributing to, reduced immune responses to H5N1 vaccine among RV subjects.
Assuntos
Anticorpos Antivirais/imunologia , Virus da Influenza A Subtipo H5N1/imunologia , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Estações do Ano , Vacinação , Feminino , Humanos , Imunogenicidade da Vacina , Masculino , Avaliação de Resultados em Cuidados de Saúde , Pontuação de PropensãoRESUMO
BACKGROUND: Human microbiome research has the potential to transform the practice of medicine, fundamentally shifting the ways in which we think not only about human health, illness and disease, but also about clinical practice and public health interventions. Drawing from a larger qualitative study on ethical, legal and social dimensions of human microbiome research, in this article, we document perspectives related to the translation of human microbiome research into clinical practice, focusing particularly on implications for health, illness and disease. METHODS: We conducted 60 in-depth, semi-structured interviews (2009-2010) with 63 researchers and National Institutes of Health project leaders ('investigators') involved with human microbiome research. The interviews explored a range of ethical, legal and social implications of human microbiome research, including investigators' perspectives on potential strategies for translating findings to clinical practice. Using thematic content analysis, we identified and analyzed emergent themes and patterns. RESULTS: We identified 3 themes: (1) investigators' general perspectives on the clinical utility of human microbiome research, (2) investigators' perspectives on antibiotic use, overuse and misuse, and (3) investigators' perspectives concerning future challenges of translating data to clinical practice. CONCLUSION: The issues discussed by investigators concerning the clinical significance of human microbiome research, including embracing a new paradigm of health and disease, the importance of microbial communities, and clinical utility, will be of critical importance as this research moves forward.
Assuntos
Pesquisa Biomédica , Microbiota , Pesquisadores , Antibacterianos/administração & dosagem , HumanosRESUMO
Erythrocyte binding antigen region II (EBA-175) is a conserved antigen of Plasmodium falciparum that is involved in binding of the parasite to the host's erythrocytes. We evaluated the safety and immunogenicity of a recombinant EBA-175 vaccine with aluminum phosphate adjuvant in healthy young adults living in the United States. Eighteen subjects/group received ascending doses (5, 20, 80, or 160 µg) of the vaccine at 0, 1, and 6 months; 8 subjects received placebo. Most of the injection site and systemic reactions were mild to moderate in intensity. After 2 or 3 doses of the vaccine at any concentration, antibody levels measured by enzyme-linked immunosorbent assay were significantly higher than those for the placebo group. Sera from subjects who received 3 doses of the vaccine at any concentration inhibited the growth of erythrocyte-stage P. falciparum at low levels compared to sera from placebo recipients or preimmune sera. In conclusion, the EBA-175 vaccine with adjuvant was safe and immunogenic in malaria-naïve subjects.
Assuntos
Antígenos de Protozoários/efeitos adversos , Antígenos de Protozoários/imunologia , Vacinas Antimaláricas/efeitos adversos , Vacinas Antimaláricas/imunologia , Malária Falciparum/prevenção & controle , Proteínas de Protozoários/efeitos adversos , Proteínas de Protozoários/imunologia , Adjuvantes Imunológicos/administração & dosagem , Adolescente , Adulto , Compostos de Alumínio/administração & dosagem , Anticorpos Antiprotozoários/sangue , Antígenos de Protozoários/administração & dosagem , Ensaio de Imunoadsorção Enzimática , Feminino , Experimentação Humana , Humanos , Imunização Secundária/métodos , Vacinas Antimaláricas/administração & dosagem , Masculino , Fosfatos/administração & dosagem , Placebos/administração & dosagem , Plasmodium falciparum/crescimento & desenvolvimento , Plasmodium falciparum/imunologia , Proteínas de Protozoários/administração & dosagem , Estados Unidos , Vacinação/métodos , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/efeitos adversos , Vacinas Sintéticas/imunologia , Adulto JovemRESUMO
Alternative substrates for influenza vaccine production are needed to ensure adequate supplies. We evaluated the relative safety and immunogenicity of recombinant hemagglutinin (rHA) or trivalent inactivated vaccine (TIV) among 869 > or =65-year-old subjects in a randomized clinical trial. Virologic surveillance for influenza-like illness (ILI) was conducted during the 2006-2007 epidemic. Vaccines were well tolerated. Seroconversion rates vs. influenza A/H1N1 and H3N2 antigens were superior in the rHA group, but were inferior vs. influenza B; however, results for influenza B are confounded since the vaccine antigens were different. ILI frequencies were low and similar in both groups. Studies assessing relative immunogenicity of vaccines using identical B Ags are warranted.
Assuntos
Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Vacinas contra Influenza/imunologia , Proteínas Recombinantes/imunologia , Idoso , Humanos , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/efeitos adversos , Estudos Multicêntricos como Assunto , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/efeitos adversos , Vacinas de Produtos Inativados/imunologia , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/efeitos adversos , Vacinas Sintéticas/imunologiaRESUMO
We evaluated the safety, reactogenicity and immunogenicity of escalating doses of a new Francisella tularensis Live Vaccine Strain (LVS) lot by scarification (SCAR) or subcutaneously (SQ) in humans. Subjects (N=10/group) received one dose of LVS via SCAR at 10(5),10(7) or 10(9)cfu/ml or SQ at 10(2), 10(3),10(4) or 10(5)cfu/ml; 14 subjects received placebo. All doses/routes were well tolerated. When compared to placebo, vaccination with 10(7) SCAR and 10(9) SCAR resulted in significantly higher serologic response frequencies, as measured by ELISA for IgG, IgM, IgA and microagglutination; whereas vaccination with 10(5) SCAR, 10(7) SCAR 10(9) SCAR and 10(5) SQ elicited a significantly higher interferon-gamma response frequency.
Assuntos
Vacinas Bacterianas/efeitos adversos , Vacinas Bacterianas/imunologia , Francisella tularensis/imunologia , Adolescente , Adulto , Anticorpos Antibacterianos/sangue , Vacinas Bacterianas/administração & dosagem , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Injeções Subcutâneas , Interferon gama/sangue , Masculino , Placebos/administração & dosagem , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/efeitos adversos , Vacinas Atenuadas/imunologia , Adulto JovemRESUMO
BACKGROUND: The incidence and severity of herpes zoster and postherpetic neuralgia increase with age in association with a progressive decline in cell-mediated immunity to varicella-zoster virus (VZV). We tested the hypothesis that vaccination against VZV would decrease the incidence, severity, or both of herpes zoster and postherpetic neuralgia among older adults. METHODS: We enrolled 38,546 adults 60 years of age or older in a randomized, double-blind, placebo-controlled trial of an investigational live attenuated Oka/Merck VZV vaccine ("zoster vaccine"). Herpes zoster was diagnosed according to clinical and laboratory criteria. The pain and discomfort associated with herpes zoster were measured repeatedly for six months. The primary end point was the burden of illness due to herpes zoster, a measure affected by the incidence, severity, and duration of the associated pain and discomfort. The secondary end point was the incidence of postherpetic neuralgia. RESULTS: More than 95 percent of the subjects continued in the study to its completion, with a median of 3.12 years of surveillance for herpes zoster. A total of 957 confirmed cases of herpes zoster (315 among vaccine recipients and 642 among placebo recipients) and 107 cases of postherpetic neuralgia (27 among vaccine recipients and 80 among placebo recipients) were included in the efficacy analysis. The use of the zoster vaccine reduced the burden of illness due to herpes zoster by 61.1 percent (P<0.001), reduced the incidence of postherpetic neuralgia by 66.5 percent (P<0.001), and reduced the incidence of herpes zoster by 51.3 percent (P<0.001). Reactions at the injection site were more frequent among vaccine recipients but were generally mild. CONCLUSIONS: The zoster vaccine markedly reduced morbidity from herpes zoster and postherpetic neuralgia among older adults.
Assuntos
Vacina contra Varicela , Herpes Zoster/prevenção & controle , Herpesvirus Humano 3 , Neuralgia/prevenção & controle , Idoso , Vacina contra Varicela/efeitos adversos , Vacina contra Varicela/imunologia , Efeitos Psicossociais da Doença , Método Duplo-Cego , Feminino , Seguimentos , Herpes Zoster/complicações , Herpes Zoster/epidemiologia , Herpesvirus Humano 3/imunologia , Humanos , Memória Imunológica , Incidência , Masculino , Pessoa de Meia-Idade , Neuralgia/virologia , Vacinas Atenuadas/efeitos adversos , Vacinas Atenuadas/imunologia , Ativação ViralRESUMO
Methods for enhancing immune responses to influenza were explored in 2 double-blind, placebo-controlled trials. Intranasal (inl) immunization with monovalent, live attenuated, cold-adapted recombinant (CR) or inactivated influenza virus (MIV) vaccine and intramuscular (im) immunization with MIV were evaluated in various combinations. Healthy susceptible adults were assigned randomly to receive 10(7.1) TCID(50) of CR (A/H1N1 or A/H3N2), homologous MIV (15 microg), or placebo inl and placebo or homologous MIV im (6 groups in each study). Serum antibody responses were greatest in groups given im vaccine (with or without inl vaccine). A 2-fold increase in nasal wash antibody response frequencies was seen in groups given combined inl (CR or MIV) and im vaccine, compared with subjects given a single im (MIV) or inl (CR or MIV) vaccine. Combined inl and im immunization is a promising approach for enhancing both local and systemic immune responses against influenza.
Assuntos
Anticorpos Antivirais/sangue , Vírus da Influenza A/imunologia , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Administração Intranasal , Adolescente , Adulto , Temperatura Baixa , Método Duplo-Cego , Humanos , Injeções Intramusculares , Vacinação , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/imunologia , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/imunologia , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/imunologiaRESUMO
Sera from six adults, collected before and after acellular pertussis vaccination, and from a placebo control were examined for the ability to elicit two bactericidal immune defenses, (i) antibody-dependent complement-mediated bacterial lysis and (ii) opsonization and phagocytosis by human neutrophils. The samples were chosen based on low preimmunization titers and strong postimmunization responses to various combinations of vaccine antigens. All but two prevaccination samples demonstrated activity indicative of complement-mediated lysis. Preimmunization activity could have been due to prior infection or childhood immunization. Immunization did not result in improved bactericidal activity for any of the individuals, and in two cases immunization caused a statistically significant decrease in complement-mediated lysis. Similarly, opsonization with the postimmunization sera failed to enhance attachment or phagocytosis of bacteria by neutrophils, and one postimmunization sample with a strong response to filamentous hemagglutinin caused an inhibition of phagocytosis that was statistically significant compared to that observed for the no-serum control. In summary, booster immunization of adults with acellular pertussis vaccines was not found to increase bactericidal activity over preimmunization levels. Identifying ways to promote bactericidal immune responses might improve the efficacy of acellular pertussis vaccines.
Assuntos
Atividade Bactericida do Sangue , Vacina contra Coqueluche/imunologia , Fatores de Virulência de Bordetella , Adenilil Ciclases/imunologia , Adesinas Bacterianas/imunologia , Adulto , Proteínas do Sistema Complemento/fisiologia , Hemaglutininas/imunologia , Humanos , Neutrófilos/imunologia , Fagocitose , Vacinação , Vacinas Acelulares/imunologiaRESUMO
The safety and immunogenicity of 2 yeast-derived, blood-stage malaria vaccines were evaluated in a phase l trial. Healthy adults were given 2 or 3 doses of alum-adsorbed vaccine containing the 19 kDa carboxy-terminal fragment of the merozoite surface protein-1 (MSP-1(19)) derived from the 3D7 or the FVO strain of Plasmodium falciparum fused to tetanus toxoid T-helper epitopes P30 and P2. The first 2 doses of MSP-1(19) were well tolerated. Hypersensitivity reactions occurred in 3 subjects after the third dose of MSP-1(19), including bilateral injection site reactions in 2 (one with generalized skin rash), and probable histamine-associated hypotension in 1. Serum antibody responses to MSP-1(19) occurred in 5/16, 9/16 and 0/8 subjects given 20 microg of MSP-1(19), 200 microg of MSP-1(19), and control vaccines (hepatitis B or Td), respectively. Both MSP-1(19) vaccines were immunogenic in humans, but changes in formulation will be necessary to improve safety and immunogenicity profiles.
Assuntos
Epitopos de Linfócito T , Vacinas Antimaláricas/imunologia , Proteína 1 de Superfície de Merozoito/imunologia , Fragmentos de Peptídeos/imunologia , Plasmodium falciparum/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Toxoide Tetânico/imunologia , Vacinas Sintéticas/imunologia , Adolescente , Adulto , Animais , Anticorpos Antiprotozoários/sangue , Humanos , Ativação Linfocitária , Vacinas Antimaláricas/efeitos adversos , Pessoa de Meia-Idade , Testes CutâneosRESUMO
Immunization against pertussis after childhood previously was considered unnecessary, because severe illness and complications rarely developed in older persons. The rising incidence of pertussis among older adolescents and adults and the transmission of infection from adults to infants suggest that booster immunization may be necessary to more effectively control pertussis in all age groups. Whole cell pertussis vaccines are regarded as unsuitable for routine use in adults because of reports of frequent moderate to severe reactogenicity at the injection site and occasional systemic reactions. The introduction of safe and effective acellular pertussis vaccines provides us with an opportunity to reconsider booster immunization of adolescents and adults. Several vaccines containing purified component(s) of Bordetella pertussis have been well tolerated and highly immunogenic when given to healthy adults. A clear understanding of the impact of pertussis in adolescents and adults will help to define the need for booster immunization after childhood.
Assuntos
Vacina contra Coqueluche , Vacinação/tendências , Vacinas de Produtos Inativados , Coqueluche/prevenção & controle , Adolescente , Adulto , Fatores Etários , Humanos , Vacina contra Coqueluche/efeitos adversos , Vacinas de Produtos Inativados/efeitos adversosRESUMO
The safety and immunogenicity of 5 acellular pertussis vaccines (ACVs) were compared in a multicenter, randomized, double-blind trial. A total of 481 healthy adults were given a single intramuscular booster dose of ACV or placebo. Three different dose levels were tested for 4 ACVs: full strength (the dose level proposed for infant immunization), one-third strength, and one-tenth strength. For 1 multicomponent vaccine, only the pertussis toxoid dose level varied. Minor injection site reactions were common and similar in frequency among vaccinated groups. Late-onset injection site reactions were seen in all ACV groups. Dose-related increases in mean antibody titers against vaccine antigens were seen after immunization with all ACVs. Antibody responses against antigens not known to be present in the vaccines were detected after immunization with 4/5 ACVs. Antibody levels fell significantly during the year after immunization. These data support evaluation of ACVs for broader use among adolescents and adults.
Assuntos
Anticorpos Antibacterianos/sangue , Bordetella pertussis/imunologia , Vacina contra Coqueluche/efeitos adversos , Vacina contra Coqueluche/imunologia , Adolescente , Adulto , Relação Dose-Resposta a Droga , Relação Dose-Resposta Imunológica , Método Duplo-Cego , Humanos , Imunização Secundária , Pessoa de Meia-Idade , Toxoides/imunologiaRESUMO
The pathogenesis of pertussis, and the epidemiology and clinical manifestations of pertussis after childhood are reviewed as a background for a discussion of recent clinical trials of acellular pertussis vaccines in adults, and the vaccines' potential for routine use in adolescents and adults.
Assuntos
Vacina contra Coqueluche/administração & dosagem , Vacina contra Coqueluche/imunologia , Coqueluche/prevenção & controle , Adulto , Bordetella pertussis/imunologia , Ensaios Clínicos como Assunto , Humanos , Imunização Secundária , Coqueluche/epidemiologiaRESUMO
Inactivated influenza virus vaccines (IVVs) are used for prevention of influenza and its complications. Present vaccines are immunogenic, of low reactogenicity, and protective, but protection has varied between 0% and 100%. Increasing the dose of hemagglutinin and neuraminidase antigens with purified proteins significantly increased serum and nasal antibody responses; however, trials with newer adjuvants have not shown increased serum antibody to levels comparable with those in earlier studies using oil emulsion adjuvants. IgA antibody responses in respiratory secretions were enhanced by the respiratory administration of IVVs, but IVVs by the oral route yielded varying results. IVVs appeared less effective for pandemic influenza in 1968 than in 1957. Since IVVs will be the major preventative measure for pandemic influenza in most countries, they need to be improved to provide better protection against pandemic and interpandemic influenza. Increasing the doses of hemagglutinin and neuraminidase, using adjuvants or immunomodulators, and administering IVVs by the mucosal route could improve the performance of these vaccines.
Assuntos
Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Adjuvantes Imunológicos/farmacologia , Humanos , Imunidade nas Mucosas , Vacinas de Produtos Inativados/imunologiaRESUMO
Some reports have suggested that influenza virus vaccine is less effective in persons that have received prior annual vaccination(s) than in those receiving it for the first time. This issue was addressed by evaluating the efficacy of annual influenza vaccinations over a 5 year period in healthy adults employing commercially-available, inactivated whole-virus vaccine. Influenza vaccination had minimal effects on overall respiratory illnesses during epidemic periods. However, it reduced influenza virus shedding by an average of 38.8% and conferred protection against influenza virus infection during each epidemic. Some variation in infection rates were noted between vaccine groups given one or more than one annual immunization, and between years, but no consistent pattern of differences was noted in relation to number of successive years of vaccination. These results suggest that the current recommendation for annual influenza vaccination of persons at special risk of serious disease and complications is appropriate, but that continued efforts to improve the effectiveness of our prophylactic measures against influenza are needed.
Assuntos
Vacinas contra Influenza/administração & dosagem , Vacinas de Produtos Inativados/administração & dosagem , Adulto , Anticorpos Antivirais/sangue , Surtos de Doenças/prevenção & controle , Feminino , Humanos , Esquemas de Imunização , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Influenza Humana/virologia , Masculino , Pessoa de Meia-Idade , Orthomyxoviridae/imunologia , Orthomyxoviridae/isolamento & purificação , Estudos Prospectivos , Doenças Respiratórias/prevenção & controle , Estudos Retrospectivos , Fatores de TempoRESUMO
The reactogenicities and immunogenicities of two influenza virus vaccines were compared in a placebo-controlled clinical trial among healthy ambulatory persons > or = 65 years old (mean age, 72 years). Volunteers were assigned randomly to receive 15-, 45-, or 135-micrograms doses of monovalent influenza A/Taiwan (H1N1) hemagglutinin (HA) or subvirion (SV) vaccine intramuscularly or a placebo. Increasing doses of SV vaccine were associated with a higher rate of injection site discomfort (P < 0.05; chi-square test for linear trend), but all doses of both vaccines were well tolerated. Increasing the dose of the HA or the SV vaccine resulted in increasingly higher postimmunization levels of serum hemagglutination inhibition and neutralizing antibody levels (P < 0.001; multiple linear regression). Mean serum antibody titers at 1 month increased two- to threefold with a ninefold increase in dose; the frequencies of fourfold or greater rises in titer likewise increased. An increase in the dose of the HA or the SV vaccine also resulted in increased frequencies of rises in immunoglobulin A or G antibody titers in nasal wash specimens. The frequencies increased approximately twofold for each vaccine with a ninefold increase in the dose. These data suggest that increasing the HA vaccine dose is a promising approach to the development of improved influenza virus vaccines for use in elderly people.
Assuntos
Anticorpos Antivirais/biossíntese , Anticorpos Antivirais/imunologia , Hemaglutininas Virais/imunologia , Vacinas contra Influenza/classificação , Vacinas contra Influenza/imunologia , Idoso , Idoso de 80 Anos ou mais , Relação Dose-Resposta Imunológica , Feminino , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Humanos , Masculino , Vacinas Atenuadas/imunologiaRESUMO
The immunogenicity and toxicity of a purified influenza virus (N2) neuraminidase vaccine (NAV) were investigated in 88 human subjects aged 18-40, and compared to response to a conventional trivalent influenza vaccine, Fluogen (Parke-Davis). NAV doses ranged from 2.6 to 69.9 micrograms and were given intramuscularly. Serologic neuraminidase-inhibiting (NI) and neuraminidase-specific ELISA responses in this N2-primed population were roughly proportional to the dose administered. Maximal response was seen in 14-21 days and NI antibody titers persisted unabated for the 6-month post-vaccination follow-up period. All doses were well tolerated with respect to local and systemic reactions. NI tests performed with the putative (1975) priming N2 antigen demonstrated anamnestic response but did not reveal responses not already shown with the homologous (1992) antigen. Response to this purified, non-adjuvanted preparation encourages continuing investigation of the induction of infection-permissive immunity with influenza virus neuraminidase.
Assuntos
Vírus da Influenza A/imunologia , Vacinas contra Influenza/imunologia , Neuraminidase/imunologia , Adolescente , Adulto , Formação de Anticorpos , Especificidade de Anticorpos , Cromatografia de Afinidade , Humanos , Vacinas contra Influenza/efeitos adversosAssuntos
Tosse/etiologia , Dor/etiologia , Coqueluche/complicações , Criança , Feminino , Humanos , Pessoa de Meia-Idade , Pleura , Coqueluche/diagnósticoRESUMO
A trivalent cold-adapted recombinant (CR) influenza virus vaccine containing types A and B viruses was compared with monovalent vaccines of each virus in a double-blind, placebo-controlled trial. Adults with a wide range of preexisting antibody titers received one 0.5-mL dose intranasally of trivalent vaccine; monovalent A/H1N1, A/H3N2, or B vaccine; or placebo. All vaccines were well tolerated. Serum antibody response frequencies and postvaccination geometric mean antibody titers were similar for recipients of trivalent or the corresponding monovalent vaccine for each of the vaccine components. Stepwise logistic regression analysis of the antibody responses of trivalent vaccine recipients demonstrated that response to one vaccine virus did not adversely affect the likelihood of response to the other viruses. This study failed to find serologic evidence of interference between vaccine viruses, suggesting that trivalent CR influenza virus vaccine may be useful for preventing influenza in adult populations.
Assuntos
Anticorpos Antivirais/sangue , Vírus da Influenza A/imunologia , Vacinas contra Influenza/imunologia , Vacinas Sintéticas/imunologia , Aclimatação , Adolescente , Adulto , Análise de Variância , Formação de Anticorpos , Temperatura Baixa , Feminino , Testes de Inibição da Hemaglutinação , Humanos , Vírus da Influenza A/fisiologia , Masculino , Testes de NeutralizaçãoRESUMO
The role of adults as reservoirs of pertussis infections and as victims of symptomatic disease has recently been recognized. Waning immunity after routine pertussis immunization in childhood appears to contribute to this problem. The expanded knowledge of the components of the Bordella pertussis organism has led to the production of new vaccines consisting of one or more bacterial components. These vaccines have been found to be safe and immunogenic in adults. It is likely that within the next several years the general use of acellular pertussis vaccines for the routine immunization of adolescents and adults will be recommended.