Respuesta inmune y alergia a vacunas / Immune response and allergies to vaccines

Las vacunas son altamente efectivas en prevenir enfermedades infecciosas a través del desarrollo en el individuo de una respuesta inmune protectora, sin desarrollar la enfermedad. Los distintos tipos de vacunas producen diferentes tipos de respuestas inmunes y variadas estrategias se han desarrollado para mejorar esta respuesta. El sistema inmune sufre cambios con la edad y esta inmunosenecencia altera la capacidad de responder frente a ellas. Por otro lado, si bien el sistema inmune puede reconocer elementos presentes en las vacunas y montar respuestas de hipersensibilidad ante ellos, las alergias a las vacunas son raras, teniendo que distinguirlas adecuadamente de otro tipo de reacciones. En caso que un paciente presente una reacción compatible con alergia, es importante conocer todos los componentes de la vacuna para realizar un estudio adecuado.

Vaccines are highly effective in preventing infectious diseases through the development in the individual a protective immune response, without developing the disease. Different types of vaccines produce different types of immune responses, and varied strategies have been developed to improve this response. The immune system undergoes changes with age, and this inmunosenescence alters the ability to respond to them. On the other hand, although the immune system can recognize elements present in vaccines and establish hypersensitivity responses to them, vaccine allergies are rare, having to properly distinguish them from other types of reactions. In the event that a patient has an allergy-compatible reaction, it is important to know all the components of the vaccine to conduct a proper study.

Assessment of the pathogenicity of cell-culture-adapted Newcastle disease virus strain Komarov

Newcastle disease vaccines hitherto in vogue are produced from embryonated chicken eggs. Egg-adapted mesogenic vaccines possess several drawbacks such as paralysis and mortality in 2-week-old chicks and reduced egg production in the egg-laying flock. Owing to these possible drawbacks, we attempted to reduce the vaccine virulence for safe vaccination by adapting the virus in a chicken embryo fibroblast cell culture (CEFCC) system. Eighteen passages were carried out by CEFCC, and the pathogenicity was assessed on the basis of the mean death time, intracerebral pathogenicity index, and intravenous pathogenicity index, at equal passage intervals. Although the reduction in virulence demonstrated with increasing passage levels in CEFCC was encouraging, 20% of the 2-week-old birds showed paralytic symptoms with the virus vaccine from the 18^th(final) passage. Thus, a tissue-culture-adapted vaccine would demand a few more passages by CEFCC in order to achieve a complete reduction in virulence for use as a safe and effective vaccine, especially among younger chicks. Moreover, it can be safely administered even to unprimed 8-week-old birds.

Oral live attenuated human rotavirus vaccine (RotarixTM) offers sustained high protection against severe G9P[8] rotavirus gastroenteritis during the first two years of life in Brazilian children

In a large Phase III trial conducted in 10 Latin American countries, the safety and efficacy of the live attenuated monovalent rotavirus vaccine RIX4414 was evaluated in 15,183 healthy infants followed up during the first two years of life. Belém was the only site in Brazil included in this multicentre trial. The study in Belém included a subset of 653 infants who were followed up until 24 months of age for protection against severe rotavirus gastroenteritis. These subjects were randomly assigned in a 1:1 ratio to receive two doses of vaccine (n = 328) or two doses of placebo (n = 325) at approximately two and four months of age. Of the 653 enrolled infants, 23 dropped out during the study period. For the combined two-year period, the efficacy of RIX4414 was 72.3% [95% confidence interval (CI) 37.5-89.1%] against severe rotavirus-related gastroenteritis, reaching a protection rate of 81.8% (95% CI 36.4-96.6%) against circulating wild-type G9 rotavirus strains. It is concluded that two doses of RIX4414 are highly efficacious against severe rotavirus gastroenteritis in Belém during the first two years of life and provide high protection against the worldwide emergence and spread of G9P[8] strains.

Vacuna contra la fiebre hemorrágica argentina Candid#1 producida en la Argentina: Inmunogenicidad y seguridad / Candid#1 vaccine against Argentine Hemorrhagic Fever produced in Argentina: Immunogenicity and safety

Se realizó un estudio clínico en 946 voluntarios humanos sanos, donde se comparó la vacuna Candid#1 producida en Argentina con la elaborada en EE.UU., que había sido utilizada en estudios previos. Como objetivo primario se evaluó la equivalencia en la eficacia utilizando como marcador subrogante a la inmunogenicidad medida por detección de anticuerpos neutralizantes. Como objetivo secundario se evaluó la equivalencia en inocuidad comparando las tasas de reacciones adversas. Ambas vacunas mostraron una tasa equivalente de inmunogenicidad ligeramente superior al 95.5%, que es la eficacia estimada para Candid #1 en estudios previos. No se observaron eventos adversos graves relacionados con la vacuna. Los eventos adversos generales considerados relacionados fueron de escasa significación clínica y de resolución espontánea o con tratamiento sintomático; se presentaron en los receptores de ambas vacunas en tasas equivalentes (29.9% para la vacuna fabricada en la Argentina y 35.0% para la fabricada en EE.UU.), e incluyeron: cefalea, decaimiento, mialgias, plaquetopenia leve (< 150 000 plaquetas/mm³), náuseas y/o vómitos, leucopenia leve (< 4 000 blancos/mm³), fiebre, dolor retroocular, mareos, microhematuria, lumbalgia y exantema. Estos resultados indican que la vacuna Candid #1 elaborada en la Argentina es equivalente a la elaborada en los EE.UU. Este estudio permitió el registro del biológico producido en la Argentina ante la autoridad regulatoria del país (ANMAT).

A clinical study in 946 human volunteers was done to compare Candid #1 vaccine manufactured in Argentina with the vaccine produced in USA that had been previously used. The efficacy was evaluated using immunogenicity measured by the detection of neutralizing antibodies as a subrogate marker. Safety was evaluated comparing the rate of adverse events. Both vaccines showed a comparable rate of seroconversion, slighty higher than the efficacy estimated from previous studies (95.5%). There were no severe adverse events related to the vaccines. The general events considered related to the vaccines were not clinically relevant and disappeared either spontaneously or with symptomatic treatment. Similar rates of adverse events (29.9% for the Argentine vaccine and 35.0% for the USA vaccine) were found for both vaccines. These included: headache, weakness, myalgias, mild low blood cell (< 4 000/mm³) and platelet (< 150 000/mm³) counts, nausea and/or vomiting, fever, retroocular pain, dizziness, microhematuria, low backache and exantema. These results indicate that the vaccine Candid#1 manufactured in Argentina is equivalent to the manufactured in USA. These results allowed the National Institute of Human Viral Diseases (INEVH) to register the vaccine produced locally under the National Regulatory Authority (ANMAT).

Immunogenicity and safety of Abhay M and M-vac vaccines in healthy infants: a phase III multicentric randomized single blind trial.

OBJECTIVE: To study immunogenicity and safety of Abhay M and M-Vac vaccines in prevention of measles in healthy infants. METHODS: In a randomized, single blind, comparative, multi-centric phase III trial, a total of 600 healthy infants between 9 - 15 months of age were recruited in the study from seven participating sites during five months. The block randomization design was used for randomizing the subjects into 2 vaccine groups (Investigational Vaccine - Abhay M and Control Vaccine - M-Vac) in the ratio 2:1. At base line (visit 1) a venous blood sample 1.5 ml was collected and subjects were then administered a single dose 0.5 ml of measles vaccine (Abhay M or M-Vac vaccine) subcutaneously according to randomization. Following administration of vaccine, subjects were observed closely for 30 - 60 minutes at the study hospitals for local reactions and systemic events. At visit 2 (follow up visit) another venous blood sample 1.5 ml was collected and the paired sera (both pre and post vaccination serum) were tested concurrently. Safety and immunogenicity were assessed through follow-up of adverse events and anti measles antibody response respectively. RESULTS: Overall 95.7 % seroconversion was achieved in both the groups, 96% in Abhay M vaccine group and 95.1%. in M-Vac vaccine group. There were no statistically significant differences in the observed seroconversion rates. In Abhay M vaccine group, the pre vaccination geometric mean titers (GMT) significantly increased from 35.5 mIU/ml to 486.9 mIU/ml after vaccination. The observed significant increase of GMT in M-Vac vaccine group was from 33.3 mIU/ml to 375.8 mIU/ml. Overall 459 (82.5%) out of 556 subjects were seroprotected after vaccination i.e. > or equal to [corrected] 200 mIU/ml (Protective levels). Of the 459 seroprotected, 315 (84.9%) subjects were in Abhay M vaccine group and 144 (77.8%) subjects were in M-Vac vaccine group. The frequencies of the reported local and general symptoms were similar between the Abhay M vaccine group and M-Vac vaccine group. CONCLUSION: Human Biologicals Institute's Abhay M vaccine is equally immunogenic and as safe as M-Vac vaccine when administered to healthy infants in single dose schedule.

Segurança, imunogenicidade e eficácia protetora de duas doses da vacina RIX4414 contendo rotavírus atenuado de origem humana / Safety, immunogenicity, and protective efficacy of two doses of RIX4414 live attenuated human rotavirus vaccine in healthy Brazilian infants

OBJETIVO: Determinar a segurança, imunogenicidade e eficácia de duas doses da vacina contra o rotavírus em lactentes brasileiros saudáveis. MÉTODOS: Foi realizado um estudo randomizado, multicêntrico, duplo-cego e controlado por placebo no Brasil, México e Venezuela. Os lactentes receberam duas doses orais de vacina ou placebo aos 2 e 4 meses de idade, juntamente com as imunizações de rotina, exceto a vacina oral contra poliomielite (VOP). O presente estudo relata apenas os resultados obtidos em Belém, Brasil, onde o número de indivíduos por grupo e os títulos da vacina viral foram os seguintes: 194 (104,7 unidades formadoras de focos - UFF), 196 (10(5,2) UFF), 194 (10(5,8) UFF) e 194 (placebo). A resposta de anticorpos anti-rotavírus (anti-RV) foi avaliada em 307 indivíduos. A gravidade clínica dos episódios de gastroenterite (GE) foi determinada através de um escore com 20 pontos, onde um valor > 11 foi considerado como GE grave. RESULTADOS: As taxas de sintomas gerais solicitados foram semelhantes tanto nos indivíduos que receberam a vacina como naqueles a quem se administrou placebo. Aos 2 meses após a segunda dose, ocorreu resposta em termos de IgA sérica para RV em 54,7 a 74,4 por cento dos vacinados. Não houve interferência na imunogenicidade das vacinas de rotina. A eficácia da vacina contra qualquer gastroenterite por rotavírus (GERV) foi de 63,5 por cento (IC95 por cento 20,8-84,4) para a maior concentração (10(5,8) UFF). A eficácia foi de 81,5 por cento (IC95 por cento 44,5-95,4) contra GERV grave. Em sua maior concentração (10(5,8) UFF), a RIX4414 conferiu uma proteção de 79,8 por cento (IC95 por cento 26,4-96,3) contra GERV grave causada pela amostra G9. CONCLUSÕES: A RIX4414 foi altamente imunogênica com baixa reatogenicidade, e não interferiu na resposta sérica à difteria, tétano, coqueluche, hepatite B e antígenos Hib. Duas doses da RIX4414 conferiram proteção significativa contra a GE grave causada pelo RV.

OBJECTIVE: To determine the safety, immunogenicity and efficacy of two doses of rotavirus vaccine in healthy Brazilian infants. METHODS: A randomized, multicenter, double-blind, placebo-controlled trial was conducted in Brazil, Mexico and Venezuela. Infants received two oral doses of vaccine or placebo at 2 and 4 months of age, concurrently with routine immunizations, except for oral poliomyelitis vaccine (OPV). This paper reports results from Belém, Brazil, where the number of subjects per group and the viral vaccine titers were: 194 (10(4.7) focus forming units - FFU), 196 (10(5.2) FFU), 194 (10(5.8) FFU) and 194 (placebo). Anti-rotavirus (anti-RV) antibody response was assessed in 307 subjects. Clinical severity of gastroenteritis episodes was measured using a 20-point scoring system with a score of > 11 defined as severe GE. RESULTS: The rates of solicited general symptoms were similar in vaccine and placebo recipients. At 2 months after the second dose, a serum IgA response to RV occurred in 54.7 to 74.4 percent of vaccinees. No interference was seen in the immunogenicity of routine vaccines. Vaccine efficacy against any rotavirus gastroenteritis (RVGE) was 63.5 percent (95 percentCI 20.8-84.4) for the highest concentration (10(5.8) FFU). Efficacy was 81.5 percent (95 percentCI 44.5-95.4) against severe RVGE. At its highest concentration (10(5.8) FFU), RIX4414 provided 79.8 percent (95 percentCI 26.4-96.3) protection against severe RVGE by G9 strain. CONCLUSIONS: RIX4414 was highly immunogenic with a low reactogenicity profile and did not interfere with seroresponse to diptheria, tetanus, pertussis, hepatitis B and Hib antigens. Two doses of RIX4414 provided significant protection against severe GE caused by RV.

La prevención de la influenza: recomendaciones para la temporada de 2005-2006 / Preventing influenza: recommendations for the 2005-2006 season

Influenza is a serious health problem worldwide due to the epidemics and pandemics that it periodically causes. The Advisory Committee on Immunization Practices (ACIP) of the United States of America recently published updated recommendations for influenza prevention and control for the 2005-2006 season. Many of these guidelines are of interest to the countries of the Region of the Americas, particularly those related to vaccination, which is the mainstay for preventing and controlling this disease. Various changes have been made in the recommendations that were published in 2004. First, the ACIP recommends vaccination against influenza for persons with any condition (e.g., cognitive dysfunction, spinal cord injury, seizure disorder, or other neuromuscular disorder) that can compromise respiratory function or make eliminating respiratory secretions difficult or that can increase the risk for aspiration. Second, the ACIP strongly recommends that all health care workers be vaccinated against influenza annually and encourages facilities that employ health care workers to vaccinate them by using approaches that maximize immunization rates. Third, the ACIP encourages the use of both available vaccines (inactivated and live, attenuated influenza vaccine (LAIV)) for eligible persons every influenza season, especially persons in recommended target groups. When inactivated virus vaccine is in short supply, the use of LAIV is especially encouraged, if feasible, for eligible persons (including health care workers) because such use might considerably increase the availability of inactivated virus vaccine for persons in high-risk groups. Fourth, the 2005-06 trivalent vaccine virus strains are A/California/7/2004 (H3N2)-like, A/New Caledonia/20/99 (H1N1)-like, and B/Shanghai/361/2002-like antigens. For the A/California/7/2004 (H3N2)-like antigen, manufacturers may use the antigenically equivalent A/ New York/55/2004 virus, and for the B/Shanghai/361/2002-like antigen, manufacturers may use the antigenically equivalent B/Jilin/20/2003 virus or B/Jiangsu/10/2003 virus.

Immunogenicity and adverse effects of live attenuated varicella vaccine (Oka-strain) in children with chronic liver disease.

Varicella infection may cause significant morbidity and mortality especially in immunocompromised persons. Children with chronic liver disease who undergo liver transplantation and need long term immunosuppressive therapy are at risk to acquire the infection. Twenty-nine children (aged 1-12 years) with chronic liver disease were enrolled to receive one dose of live attenuated varicella vaccine (Oka-strain). During the 16-week follow-up period, no vaccine-related serious adverse events were reported. Seroconversion rates at 8 weeks post vaccination were 100%. Geometric mean titer (GMT) values and seropositive rates at 16 weeks tended to relate to the clinical severity of liver disease. This study demonstrates that varicella vaccine is safe and Immunogenic in children with chronic liver disease.

The neurovirulence of flaviviruses in crab-eating monkeys (Macaca fascicularis).

The neurovirulent properties of attenuated dengue-2 and yellow fever (YF) vaccines, dengue-2 (DEN-2) and Japanese encephalitis (JE) viruses were studied in crab-eating monkeys (Macaca fascicularis). Number of central nervous system sites (as proportion affected) with neurovirulence (NV) lesions were compared. The results indicate that these monkeys reliably developed NV-lesion when inoculated with either JE or YF vaccine viruses (87%). NV-lesions occurred in a minority when inoculated with DEN-2 vaccine virus, were of minimal severity (9%), were probably biologically insignificant, and were of equal or less severity than lesions produced by its parental virus (10%).