N. M. Frazatti-Gallina

Cost of production of live attenuated dengue vaccines: A case study of the Instituto Butantan, Sao Paulo, Brazil

BACKGROUNDnA vaccine to prevent dengue disease is urgently needed. Fortunately, a few tetravalent candidate vaccines are in the later stages of development and show promise. But, if the cost of these candidates is too high, their beneficial potential will not be realized. The price of a vaccine is one of the most important factors affecting its ultimate application in developing countries. In recent years, new vaccines such as those for human papilloma virus and pneumococcal disease (conjugate vaccine) have been introduced with prices in developed countries exceeding

Immunodiagnosis in cerebrospinal fluid of cerebral toxoplasmosis and HIV-infected patients using Toxoplasma gondii excreted/secreted antigens ☆

50 per dose. These prices are above the level affordable by developing countries. In contrast, other vaccines such as those against Japanese encephalitis (SA14-14-2 strain vaccine) and meningitis type A have prices in developing countries below one dollar per dose, and it is expected that their introduction and use will proceed more rapidly. Because dengue disease is caused by four related viruses, vaccines must be able to protect against all four. Although there are several live attenuated dengue vaccine candidates under clinical evaluation, there remains uncertainty about the cost of production of these tetravalent vaccines, and this uncertainty is an impediment to rapid progress in planning for the introduction and distribution of dengue vaccines once they are licensed.nnnMETHODnWe have undertaken a detailed economic analysis, using standard industrial methodologies and applying generally accepted accounting practices, of the cost of production of a live attenuated vaccine, originally developed at the US National Institutes of Health (National Institute of Allergy and Infectious Diseases), to be produced at the Instituto Butantan in Sao Paulo, Brazil. We determined direct costs of materials, direct costs of personnel and labor, indirect costs, and depreciation. These were analyzed assuming a steady-state production of 60 million doses per year.nnnRESULTSnAlthough this study does not seek to compute the price of the final licensed vaccine, the cost of production estimate produced here leads to the conclusion that the vaccine can be made available at a price that most ministries of health in developing countries could afford. This conclusion provides strong encouragement for supporting the development of the vaccine so that, if it proves to be safe and effective, licensure can be achieved soon and the burden of dengue disease can be reduced.

Matricaria chamomilla CH12 decreases handling stress in Nelore calves

Cerebral toxoplasmosis is the most common neurologic opportunistic infection in HIV-infected patients. Excretory-secretory antigens (ESA) are the majority of the circulating antigens in sera from hosts with acute toxoplasmosis, and their usefulness as antigens has been shown. This study considered whether it could find anti-ESA antibodies in cerebrospinal fluid (CSF) and whether these antibodies can be markers of active infection. Samples of CSF from 270 HIV-infected patients were analyzed and divided into 3 groups according to the presence or absence of active toxoplasmosis. Group I: 99 patients with cerebral toxoplasmosis; group II: 112 patients with other opportunistic neurologic diseases and seropositive for toxoplasmosis; and group III: 59 patients with other opportunistic neurologic diseases and seronegative for toxoplasmosis. Toxoplasma gondii ESA and a crude tachyzoite antigen were used as antigens using ELISA and immunoblotting. The statistical analysis was done using the F test and unpaired Students t test. Crude tachyzoite antigen: mean ELISA-relative values ± standard error for CSF of groups I and II were 7.0 ± 0.27 and 3.9 ± 0.19, respectively. Variance analysis revealed that results of both groups of patients were statistically different (1.80, P = 0.0025). The difference between the mean results was 3.0 ± 0.3, and the Students t test value was 9.41 (P = 0.0001). Samples from groups I and II were reactive by immunoblotting, with similar intensities. In ESA-ELISA, the mean for group I was 9.0 ± 0.39. Group II showed a mean value of 2.7 ± 0.12. Both groups were statistically different (9.16, P < 0.001). However, in ESA, the difference between the mean results was higher (6.2 ± 0.39) and the Students t test value was 16.04 (P < 0.0001). Similar results were shown in immunoblotting where a CSF sample from group I reacted well with ESA, and the sample from a group II patient failed to do so. The mean ELISA-relative value of the control group (group III) was 0.5 ± 0.09 for the first antigen and 0.4 ± 0.22 for the second. ESA-ELISA and/or immunoblotting of CSF samples can be used for diagnosis of cerebral toxoplasmosis in association with clinical, serologic, and radiological information, thus providing a simple straightforward methodology, particularly suitable in countries with high prevalence of latent toxoplasmosis in the general population.

A phase I clinical trial of a new 5-valent rotavirus vaccine

Matricaria chamomilla CH12 is a phytotherapeutic or homeopathic product, which has been used to reduce stress. Here, we examined its effect on preventing handling stress in bovines. Sixty Nelore calves were randomly distributed into two equal groups. One group was administered Matricaria chamomilla CH12 in diet and the other the control was not. Animals in both groups were maintained unstressed for 30 days to adjust to the feeding system and pasture, and were then stressed by constraint on the 31th, 38th, 45th and 60th experimental days. Blood samples were taken on these days after animals had been immobilization in a trunk contention for 5 min. Stress was followed by analyzing serum cortisol levels. These peaked on the 45th day and then decreased, but not to baseline, on the 60th day. On the 45th day cortisol levels were significantly lower in animals fed Matricaria chamomilla CH12, suggesting that this product reduces stress. These effects may be a consequence of its inhibiting cortisol production and its calming and anxiolytic effects.

Efficiency of Matricaria chamomilla CH12 and number of doses of rabies vaccine on the humoral immune response in cattle.

We conducted a phase I, double-blind, placebo-controlled trial to evaluate a new 5-valent oral rotavirus vaccines safety and immunogenicity profiles. Subjects were randomly assigned to receive 3 orally administered doses of a live-attenuated human-bovine (UK) reassortant rotavirus vaccine, containing five viral antigens (G1, G2, G3, G4 and G9), or a placebo. The frequency and severity of adverse events were assessed. Immunogenicity was evaluated by the titers of anti-rotavirus IgA and the presence of neutralizing antibodies anti-rotavirus. No severe adverse events were observed. There was no difference in the frequency of mild adverse events between experimental and control groups. The proportion of seroconversion was consistently higher in the vaccine group, for all serotypes, after each one of the doses. The 5-valent vaccine has shown a good profile of safety and immunogenicity in this small sample of adult volunteers.

Probiotic increase the antirabies humoral immune response in bovine

This study evaluated the effect of Matricaria chamomilla and vaccination frequency on cattle immunization against rabies. Four groups (n = 15 /group) were treated with or without Matricaria chamomilla CH12 and vaccinated with one or two doses of rabies vaccine (30 day interval). No effect of chamomile was found on cattle immunization against rabies; however, antibody titers were protective in cattle vaccinated twice, while 93.3% of cattle vaccinated only once had titers under 0.5 UI/ml after 60 days. In conclusion, the use of chamomile did not alter the humoral immune response in cattle, and two vaccine doses are suggested for achieving protective antibody titers.

Selenium supplementation and rabies antibody titres in cattle

EnglishThe effect of a probiotic on the immune response of cattle immunized with a dose of rabies vaccine was evaluated in this study. The Nellore bovines (N= 75) were divided randomly into 5 groups: supplemented with 0, 2, 3, 4 and 8 g the probiotic (Proenzime®)/animal/day, groups Gc, G2, G3, G4 and G8 respectively, for 60 days. All the animals were immunized with a single dose of rabies vaccine on the first day of the experiment (day 0). The obtained results showed that there was significant increase (p portuguesFoi avaliado o efeito do probiotico sobre a resposta imune de bovinos imunizados com uma dose de vacina anti-rabica. Utilizou-se bovinos Nelore (N= 75) divididos randomicamente em 5 grupos: suplementados com 0, 2, 3, 4 e 8 g probiotico (Proenzime®)/bovino/dia, grupos Gc, G2, G3, G4 e G8, respectivamente, por 60 dias. Todos os animais foram imunizados com uma de vacina anti-rabica no dia zero do experimento. Os resultados obtidos mostraram que houve aumento significativo (p

Effects of selenium supplementation on serum cortisol in repeatedly handled cattle

SIR, — Regular vaccination is the most effective and inexpensive procedure for controlling rabies in cattle ([Albas and others 2005][1]). Given that selenium (Se) enhances cattle immunity to infectious diseases ([Carroll and Forsberg 2007][2]), we investigated whether Se enhances the humoral

Effect of levamisole on the humoral immune response against rabies in cattle

This study evaluated the relationship between nSe supplementation and serum cortisol in repeatedly nhandled cattle. Sixty Nellore calves were randomly ndistributed into four experimental groups, which nwere fed a mineral-protein mixture added with Se nto achieve individual daily supplementation of 0 n(Gc), 3.6 (G 3.6 ), 5.4 (G 5.4 ) and 6.4 (G 6.4 ) mg Se. nStressful handling procedures and blood sampling nwere performed on days 0, 15, 30, 60, 90 and 120. nSerum cortisol increased until day 90 and decreased non day 120, irrespective of Se supplementation. nThis finding shows that cattle reached a stress nstate but adapted. Cortisol and Se levels were not nmarkedly correlated. Serum Se increased over the ncourse of the experiment in the supplemented ngroups. However, because serum Se decreased nin Gc, it may have mobilized to form the nselenoproteins needed to remove metabolic wastes nfrom handling-related oxidative stress.

Association between handling stress in the corral and rabies antibody titers in selenium-supplemented cattle

BOVINE rabies, a fatal encephalitis caused by viruses of the genus Lyssavirus , is mainly transmitted by the common vampire bat ( Desmodus rotundus ) ([Achkar and others 2007][1]). There is no effective treatment for rabies; therefore, regular vaccination of at-risk animals is the best control