Prevalence of neutralizing antibodies against poliovirus 1, 2, and 3 in healthcare professionals aged 20-50 years / Prevalência de anticorpos neutralizantes contra poliovírus 1, 2 e 3 em profissionais de saúde de 20 a 50 anos de idade

ABSTRACT Objective: To describe the prevalence of neutralizing antibodies against poliovirus (PV1, PV2, and PV3) in blood samples of healthcare professionals aged 20 to 50 years. Methods: Health professionals who serve children at Darcy Vargas Children's Hospital and the Department of Pediatrics of Irmandade da Santa Casa de São Paulo. The sample size was calculated at 323 participants. The Mantel-Haenszel chi-square was used to verify differences between groups. The neutralization reaction detected human poliovirus antibodies. For susceptible individuals, vaccination with the inactivated+triple acellular polio vaccine was performed, and neutralizing antibodies were re-dosed after one week. Results: 333 professionals were studied - 92.8% were immune to poliovirus 1, 86.5% to poliovirus 2, and 63.3% to poliovirus 3; 37% had titers less than 1:8 for any serotype, 5;1% had titers below 1:8 for all three. Vaccination with inactivated polio vaccine was performed for susceptible participants, and neutralizing antibodies were dosed after one week, showing increased titers for all polioviruses. Conclusions: Despite the detection of a significant percentage of individuals with low poliovirus antibody titer, the challenge with vaccination demonstrated immune response compatible with poliovirus immunity.

RESUMO Objetivo: Descrever a prevalência de anticorpos neutralizantes contra poliovírus (tipos 1, 2 e 3) em amostra de sangue de profissionais de saúde com idade de 20 a 50 anos. Métodos: Profissionais de saúde que atendem crianças do Hospital Infantil Darcy Vargas e do Departamento de Pediatria da Irmandade da Santa Casa de São Paulo. O tamanho da amostra foi de 323 participantes. Os anticorpos contra poliovírus humanos foram detectados pela reação de neutralização. Para os indivíduos suscetíveis, foram administradas vacina para poliomielite inativada+tríplice e nova dosagem de anticorpos neutralizantes após uma semana. Utilizou-se o teste do qui-quadrado de Mantel-Haenszel para verificar as diferenças entre os grupos. Resultados: Foram estudados 333 profissionais - 92,8% eram imunes ao poliovírus 1; 86,5%, ao poliovírus 2; 63,57%, ao poliovírus 3; 37% apresentaram títulos inferiores a 1:8 para qualquer sorotipo; 5,1% tinham títulos abaixo de 1:8 para os três. Após a vacinação dos suscetíveis, houve elevação dos títulos para todos os poliovírus. Conclusões: Apesar da detecção de percentual significativo de indivíduos com baixo título de anticorpos para poliovírus, o desafio da vacinação demonstrou resposta imune robusta compatível.

Durability of neutralizing antibodies and T-cell response post SARS-CoV-2 infection / 医学前沿

The ongoing pandemic of Coronavirus disease 19 (COVID-19) is caused by a newly discovered β Coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). How long the adaptive immunity triggered by SARS-CoV-2 can last is of critical clinical relevance in assessing the probability of second infection and efficacy of vaccination. Here we examined, using ELISA, the IgG antibodies in serum specimens collected from 17 COVID-19 patients at 6-7 months after diagnosis and the results were compared to those from cases investigated 2 weeks to 2 months post-infection. All samples were positive for IgGs against the S- and N-proteins of SARS-CoV-2. Notably, 14 samples available at 6-7 months post-infection all showed significant neutralizing activities in a pseudovirus assay, with no difference in blocking the cell-entry of the 614D and 614G variants of SARS-CoV-2. Furthermore, in 10 blood samples from cases at 6-7 months post-infection used for memory T-cell tests, we found that interferon γ-producing CD4

Clinical characteristics and plasma antibody titer of patients with COVID-19 in Zhejiang, China / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which first affected humans in China on December 31, 2019 (Shi et al., 2020). Coronaviruses generally cause mild, self-limiting upper respiratory tract infections in humans, such as the common cold, pneumonia, and gastroenteritis (To et al., 2013; Berry et al., 2015; Chan et al., 2015). According to the Report of the World Health Organization (WHO)-China Joint Mission on COVID-19 (WHO, 2020), the case fatality rate of COVID-19 increases with age, while the rate among males is higher than that among females (4.7% and 2.8%, respectively). Since an effective vaccine and specific anti-viral drugs are still under development, passive immunization using the convalescent plasma (CP) of recovered COVID-19 donors may offer a suitable therapeutic strategy for severely ill patients in the meantime. So far, several studies have shown therapeutic efficacy of CP transfusion in treating COVID-19 cases. A pilot study first reported that transfusion of CP with neutralizing antibody titers above 1:640 was well tolerated and could potentially improve clinical outcomes through neutralizing viremia in severe COVID-19 cases (Chen et al., 2020). Immunoglobulin G (IgG) and IgM are the most abundant and important antibodies in protecting the human body from viral attack (Arabi et al., 2015; Marano et al., 2016). Our study aimed to understand the aspects of plasma antibody titer levels in convalescent patients, as well as assessing the clinical characteristics of normal, severely ill, and critically ill patients, and thus provide a basis for guiding CP therapy. We also hoped to find indicators which could serve as a reference in predicting the progression of the disease.

Pure red cell aplasia and anti-erythropoietin antibodies in patients on hemodialysis: a report of two cases and a literature review / Aplasia pura de células vermelhas e anticorpo antieritropoietina em pacientes de hemodiálise: relato de dois casos e revisão da literatura

ABSTRACT Introduction: Anemia is a frequent multifactorial complication of CKD seen in patients on dialysis derived mainly from impaired erythropoietin (EPO) production. A less common cause of anemia in individuals with CKD is pure red cell aplasia (PRCA) secondary to the production of anti-EPO antibodies. Objective: This paper aimed two describe two cases of PRCA secondary to the production of anti-EPO antibodies including choice of treatment, patient progression, and a literature review. Materials: This study included the cases of two patients with CKD on hemodialysis with severe anemia in need of specific investigation and management. Results: Patient 1 with CKD secondary to hypertension treated with EPO for 7 months showed persistent decreases in hemoglobin (Hb) levels despite the subcutaneous administration of increasing doses of EPO; the patient required recurring blood transfusions. Workup and imaging tests were negative for the main causes of anemia in individuals with CKD on dialysis. Patient 2 with CKD secondary to adult polycystic kidney disease had been taking EPO for 2 years. The patient developed severe abrupt anemia the month he was started on HD, and required recurring transfusions to treat the symptoms of anemia. Workup and imaging findings were inconclusive. Specific laboratory tests confirmed the patients had anti-EPO antibodies. After six months of immunosuppressant therapy (corticosteroids + cyclosporine) the patients were stable with Hb > 9.0 g/dl. Conclusion: PRCA is a rare condition among patients on dialysis treated with rhEPO and should be considered as a possible cause of refractory anemia. Treating patients with PRCA may be challenging, since the specific management and diagnostic procedures needed in this condition are not always readily available.

RESUMO Introdução: Anemia é complicação frequente da Doença Renal Crônica (DRC) em pacientes dialíticos. Apresenta caráter multifatorial principalmente pela insuficiente produção de eritropoietina (EPO). Situação rara causadora de anemia na DRC é Aplasia Pura de Células Vermelhas (APCV), em decorrência da produção de anticorpos anti-EPO. Objetivo: Descrever 2 casos de APCV com formação de anticorpos anti-EPO, sua abordagem clínica, evolução e revisão de literatura. Métodos: Dois pacientes em hemodiálise que desenvolveram anemia grave, necessitando investigação e manejo específico. Resultados: Paciente nº 1: feminina, 75 anos, DRC secundária à hipertensão arterial. Após 7 meses com EPO desenvolveu queda persistente em valores de hemoglobina (Hb) mesmo com incremento em doses EPO SC, necessitando transfusões de sangue recorrentes. Extensa investigação laboratorial e de imagem resultou negativa para principais causas de anemia. Paciente nº 2: masculino, 66 anos, DRC secundária à DRPA, há 2 anos em uso de EPO. No mês de entrada em HD desenvolveu anemia severa, também exigindo transfusões recorrentes para tratamento da anemia sintomática. Extensa investigação laboratorial e por imagem, sem chegar a uma conclusão definitiva. Em ambos os casos a presença de anticorpos anti-EPO foi confirmada por exames laboratoriais específicos. Terapia imunossupressora resultou em estabilização do quadro e Hb > 9,0 g/dl em ambos os pacientes, 6 meses após início do tratamento. Conclusão: APCV é condição rara entre pacientes dialíticos que recebem EPOHuR e deve ser lembrada como causa de anemia refratária. Seu manejo específico e diagnóstico laboratorial nem sempre acessível, tornando desafiadora a condução dos casos para o nefrologista.

Prevalence and titers of yellow fever virus neutralizing antibodies in previously vaccinated adults

ABSTRACT Introduction: The World Health Organization (WHO) recommends one single dose of the Yellow Fever (YF) vaccine based on studies of antibody persistency in healthy adults. We assessed the prevalence and titers of YF virus neutralizing antibodies in previously vaccinated persons aged ≥ 60 years, in comparison to younger adults. We also evaluated the correlation between antibody titers and the time since vaccination among participants who received one vaccine dose, and the seropositivity among participants vaccinated prior to or within the past 10 years. Methods: previously vaccinated healthy persons aged ≥ 18 years were included. YF virus neutralizing antibody titers were determined by means of the 50% Plaque Reduction Neutralization Test. Results: 46 persons aged ≥ 60 years and 48 persons aged 18 to 59 years were enrolled. There was no significant difference in the prevalence of YF virus neutralizing antibodies between the two groups (p = 0.263). However, titers were significantly lower in the elderly (p = 0.022). There was no correlation between YF virus neutralizing antibody titers and the time since vaccination. There was no significant difference in seropositivity among participants vaccinated prior to or within the past 10 years. Conclusions: the clinical relevance of the observed difference in YF virus neutralizing antibody titers between the two groups is not clear.

Transferência placentária e cinética de anticorpos antidengue materno transferidos em uma coorte de crianças no primeiro ano de vida / Placental transfer and kineticis of maternal transferred dengue-specific antibodies in a cohort of children during the first year

Anticorpos antidengue materno transferidos têm sido implicados na imunopatogênese da dengue grave em lactentes. Postula-se que esses anticorpos possuam um papel distinto durante os primeiros anos de vida: ao nascimento, anticorpos antidengue materno adquiridos conferem proteção, e em seguida declinam a níveis subneutralizantes capazes de facilitar a infecção pelo vírus dengue (DENV) mediante o mecanismo de ADE (Antibody dependent enhancement), aumentando o risco de ocorrência das formas graves da dengue. Estudos prospectivos conduzidos em lactentes Asiáticos têm mostrado que o pico de anticorpos materno adquiridos com a capacidade de mediar aumento da infecção pelo DENV ocorre entre o sexto e o nono mês de vida, o que correlaciona com a epidemiologia da dengue grave em lactentes dessa região. Esta tese descreve o perfil de imunidade materna antidengue e a transferência placentária de anticorpos dengue-específicos em pares mãe-cordão recrutados em um estudo de coorte prospectivo conduzido na cidade do Recife, Nordeste do Brasil. Adicionalmente, esse trabalho analisa o papel dos níveis de IgG total maternos e da imunidade antidengue materna na transferência de anticorpos ao feto. Na coorte de lactentes, a tese avalia a cinética de declínio dos anticorpos antidengue materno-transferidos e sua capacidade de mediar ADE durante os primeiros anos de vida. Níveis de IgG DENV-especifico e de anticorpos neutralizantes sorotipo específicos (DENV1-4) foram determinados em 376 pares mãe-cordão. A cinética de anticorpos materno transferidos neutralizantes e/ou mediadores de ADE foi investigada em uma subamostra das crianças inseridas na coorte. A maior parte das gestantes apresentava imunidade ao sorotipo DENV-3 (53,7 por cento) ou a combinação DENV-3/ DENV-4 (30,6 por cento)...

Maternal-fetal transferred Dengue virus (DENV)-specific antibodies have been implicated in the immunopathogenesis of dengue during infancy. These antibodies play a dual role in infants during the first year of life: first, maternally-acquired antibodies confer protection at birth, and then decline to a lower level capable of enhance DENV infection through the mechanism of ADE (antibody-dependent enhancement), increasing the chance of development of severe dengue. Prospective studies conducted in Asian infants have provided evidence that the peak of enhancing activity by maternally transferred dengue antibodies occurs between 6th to 9th month of age, which correlates with the age-related epidemiology of the dengue severe cases in this region. This thesis describes the placental transfer of dengue-specific antibodies in mother-cord pairs enrolled in a prospective cohort study carried out in the city of Recife, Northeast Brazil. Moreover, we analyze the role of maternal total IgG levels and dengue immunity in the transference of dengue-specific antibodies to the fetus. In the cohort of children, we determine the kinetics of Enhancing Activity (EA) by maternally acquired dengue antibodies during their first year of life. DENV-specific IgG and serotype-specific (DENV1-4) neutralizing antibody (Nab) levels were assessed in 376 mother-cord paired samples...

Impact of IgM Antibodies on Cross-Protection against Pneumococcal Serogroups 6 and 19 after Immunization with 7-Valent Pneumococcal Conjugate Vaccine in Children

Although it is well known that pneumococcal conjugate vaccines provide cross-protection against some vaccine-related serotypes, these mechanisms are still unclear. This study was performed to investigate the role of cross-protective IgM antibodies against vaccine-related serotypes 6A, 6C, and 19A induced in children aged 12-23 months after immunization with 7-valent pneumococcal conjugate vaccine (PCV7). We obtained serum samples from 18 Korean children aged 12-23 months after a PCV7 booster immunization. The serum IgG and IgM concentrations of serotypes 6B and 19F were measured by enzyme-linked immunosorbent assay (ELISA) in serum. The opsonic indices (OIs) against vaccine serotypes 6B and 19F and vaccine-related serotypes 6A, 6C, and 19A were determined by an opsonophagocytic killing assay (OPA) in IgM-depleted and control serum. Both IgG and IgM antibodies in ELISA and opsonic indices in OPA against serotypes 6B and 19F were demonstrated in the immune serum. IgM depletion decreased the OIs against vaccine serotypes 6B (geometric means of OIs (GMIs) of 3,009 vs. 1,396, 38% reduction) and 19F (1,117 vs. 750, 36% reduction). In addition, IgM depletion markedly decreased the OIs against vaccine-related serotypes 6A (GMIs of 961 vs. 329, 70% reduction), 6C (432 vs. 185, 72% reduction), and 19A (301 vs. 166, 58% reduction). The booster immunization PCV7 induced protective antibodies in the form of both IgG and IgM isotypes. IgM antibodies contributed to eliciting cross-protection against vaccine-related serotypes as well as against vaccine serotypes.

Rabies surveillance in bats in Northwestern State of São Paulo

Introduction Rabies is an important zoonosis that occurs in mammals, with bats acting as Lyssavirus reservoirs in urban, rural and natural areas. Rabies cases in bats have been recorded primarily in urban areas in Northwestern State of São Paulo since 1998. This study investigated the circulation of rabies virus by seeking to identify the virus in the brain in several species of bats in this region and by measuring rabies-virus neutralizing antibody levels in the hematophagous bat Desmodus rotundus. Methods From 2008 to 2012, 1,490 bat brain samples were sent to the Universidade Estadual Paulista (UNESP) Rabies Laboratory in Araçatuba, and 125 serum samples from vampire bats that were captured in this geographical region were analyzed. Results Rabies virus was detected in the brains of 26 (2%) of 1,314 non-hematophagous bats using the fluorescent antibody test (FAT) and the mouse inoculation test (MIT). None of the 176 hematophagous bat samples were positive for rabies virus when a virus detection test was utilized. Out of 125 vampire bat serum samples, 9 (7%) had levels of rabies virus neutralization antibodies (RVNAs) that were higher than 0.5IU/mL; 65% (81/125) had titers between 0.10IU/mL and 0.5IU/mL; and 28% (35/125) were negative for RVNAs using the simplified fluorescent inhibition ...

Serologic assessment of yellow fever immunity in the rural population of a yellow fever-endemic area in Central Brazil

Introduction The yellow fever epidemic that occurred in 1972/73 in Central Brazil surprised the majority of the population unprotected. A clinical-epidemiological survey conducted at that time in the rural area of 19 municipalities found that the highest (13.8%) number of disease cases were present in the municipality of Luziânia, State of Goiás. Methods Thirty-eight years later, a new seroepidemiological survey was conducted with the aim of assessing the degree of immune protection of the rural population of Luziânia, following the continuous attempts of public health services to obtain vaccination coverage in the region. A total of 383 volunteers, aged between 5 and 89 years and with predominant rural labor activities (75.5%), were interviewed. The presence of antibodies against the yellow fever was also investigated in these individuals, by using plaque reduction neutralization test, and correlated to information regarding residency, occupation, epidemiological data and immunity against the yellow fever virus. Results We found a high (97.6%) frequency of protective titers (>1:10) of neutralizing antibodies against the yellow fever virus; the frequency of titers of 1:640 or higher was 23.2%, indicating wide immune protection against the disease in the study population. The presence of protective immunity was correlated to increasing age. Conclusions This study reinforces the importance of surveys to address the immune state of a population at risk for yellow fever infection and to the surveillance of actions to control the disease in endemic areas. .

Antibodies to Interferon beta in Patients with Multiple Sclerosis Receiving CinnoVex, Rebif, and Betaferon

Treatment with interferon beta (IFN-beta) induces the production of binding antibodies (BAbs) and neutralizing antibodies (NAbs) in patients with multiple sclerosis (MS). NAbs against IFN-beta are associated with a loss of IFN-beta bioactivity and decreased clinical efficacy of the drug. The objective of this study was to evaluate the incidence and the prevalence of binding antibodies (BAbs) and neutralizing antibodies (NAbs) to IFN-beta in MS patients receiving CinnoVex, Rebif, or Betaferon. The presence of BAbs was studied in serum samples from 124 MS patients using one of these IFN-beta medications by ELISA. The NAbs against IFN-beta were measured in BAb-positive MS patients receiving IFN-beta using an MxA gene expression assay (real-time RT-PCR). Of the 124 patients, 36 (29.03%) had BAbs after at least 12 months of IFN-beta treatment. The proportion of BAb+ was 38.1% for Betaferon, 21.9% for Rebif, and 26.8% for CinnoVex. Five BAb-positive MS patients were lost to follow-up; thus 31 BAb-positive MS patients were studied for NAbs. NAbs were present in 25 (80.6%) of BAb-positive MS patients receiving IFN-beta. In conclusion, the three IFN-beta preparations have different degrees of immunogenicity.

Comparison of Immune Response by Virus Infection and Vaccination to 2009 Pandemic Influenza A/H1N1 in Children

We aimed to compare the immune response induced by natural infection with 2009 pandemic influenza A/H1N1 (pH1N1) virus and by monovalent pH1N1 vaccination in children and adolescents. This cross-sectional clinical study was conducted at 3 hospitals in Korea from February to May 2010. A total of 266 healthy subjects aged from 6 months to 18 yr were tested for the presence of the antibody against pH1N1 using hemagglutination inhibition (HI) test. Information about pH1N1 vaccination and laboratory-confirmed pH1N1 infection history was obtained. The overall rate of HI titers of > or = 1:40 against pH1N1 was 38.7%, and the geometric mean titer (GMT) was 20.5. Immunogenicity of pH1N1 vaccination only was reflected by a 41.1% of seroprotection rate and a GMT of 22.5. Immunogenicity of natural infection only was reflected by a 61.0% of seroprotection rate and a GMT of 40.0. GMT was significantly higher in the subjects of natural infection group than in the subjects of pH1N1 vaccination group (P < 0.001). The immune responses induced by natural pH1N1 infection exceed those induced by pH1N1 vaccinations.

Neutralising antibodies for West Nile virus in horses from Brazilian Pantanal

Despite evidence of West Nile virus (WNV) activity in Colombia, Venezuela and Argentina, this virus has not been reported in most South American countries. In February 2009, we commenced an investigation for WNV in mosquitoes, horses and caimans from the Pantanal, Central-West Brazil. The sera of 168 horses and 30 caimans were initially tested using a flaviviruses-specific epitope-blocking enzyme-linked immunosorbent assay (blocking ELISA) for the detection of flavivirus-reactive antibodies. The seropositive samples were further tested using a plaque-reduction neutralisation test (PRNT90) for WNV and its most closely-related flaviviruses that circulate in Brazil to confirm the detection of specific virus-neutralising antibodies. Of the 93 (55.4 percent) blocking ELISA-seropositive horse serum samples, five (3 percent) were seropositive for WNV, nine (5.4 percent) were seropositive for St. Louis encephalitis virus, 18 (10.7 percent) were seropositive for Ilheus virus, three (1.8 percent) were seropositive for Cacipacore virus and none were seropositive for Rocio virus using PRNT90, with a criteria of > four-fold antibody titre difference. All caimans were negative for flaviviruses-specific antibodies using the blocking ELISA. No virus genome was detected from caiman blood or mosquito samples. The present study is the first report of confirmed serological evidence of WNV activity in Brazil.

Evaluation of enterovirus 71 immune status in São Paulo state, Brazil / Avaliação da situação imunitária contra enterovírus 71 no estado de São Paulo, Brasil

Antibodies to Enterovirus 71 (EV71) were evaluated in São Paulo State during 1999-2005. The titer of neutralizing antibodies against EV71 was determined by microneutralization assay, and a titer of > 1:8 was defined as indicative of protected immunity. Neutralizing antibodies to EV71 were observed in 12.4 percent (55/442) of sera samples, a low protective rate, suggesting that EV71 infection is uncommon in this region, but that there is a relatively high susceptibility to EV71 related diseases, which is worrying considering the recent Asian outbreaks. Also, a significant location-specific difference in seropositivity was observed. Neutralizing antibodies to EV71 were observed in 8.7 percent (21/241) of São Paulo metropolitan area sera samples, and 16.9 percent (34/201) of the sera samples from other municipalities. A high number of Brazilian residents live in country and coastal areas without adequate access to piped water or sanitation. This situation may contribute to the EV71 dissemination in these zones. The analysis of environmental samples could possibly make a valuable contribution to studies on the epidemiology of EV71.

Anticorpos para Enterovírus 71 (EV71) foram avaliados no Estado de São Paulo durante 1999-2005. O título de anticorpos neutralizantes contra EV71 foi determinado pelo ensaio microneutralização, e um título de > 1:8 foi definido como indicador de imunidade protetora. Anticorpos neutralizantes para EV71 foram observados em 12,4 por cento (55/442) das amostras de soro, uma baixa taxa de proteção, sugerindo que a infecção pelo EV71 é incomum nesta região e que existe alta susceptibilidade a doenças relacionadas ao EV71, o que é preocupante considerando os recentes surtos asiáticos. Ainda, foi observada diferença significativa na soropositividade em relação à localização, onde 8,7 por cento (21/241) e 16,9 por cento (34/201) das amostras provenientes da região metropolitana de São Paulo, e demais municípios, respectivamente, apresentaram anticorpos neutralizantes para EV71. Um grande número de brasileiros vive em áreas rurais e à beira-mar, sem acesso adequado à água encanada ou saneamento. Essa situação pode contribuir para a disseminação de EV71 nessas regiões. A análise de amostras ambientais poderia gerar contribuição valiosa para estudos sobre a epidemiologia da EV71.

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).