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The Butantan Institute: History and Future Perspectives


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The Butantan Institute, as one of Brazil's most prestigious scientific institutions, generates new knowledge through scientific research, develops and produces immunobiological and biopharmacological products of interest to public health, educates and trains human resources in the areas of science and technology, and seeks to stimulate scientific knowledge and understanding among the general population. With 113 years of existence marked by numerous technological advances directed towards public health issues, the Butantan Institute is considered one of the major scientific centers in the world.
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Historical Profiles and Perspectives
The Butantan Institute: History and Future Perspectives
Marcelo De Franco*, Jorge Kalil
Instituto Butantan, Sa
˜o Paulo, Sa
˜o Paulo, Brazil
The Butantan Institute, as one of
Brazil’s most prestigious scientific institu-
tions, generates new knowledge through
scientific research, develops and produces
immunobiological and biopharmacologi-
cal products of interest to public health,
educates and trains human resources in
the areas of science and technology, and
seeks to stimulate scientific knowledge and
understanding among the general popula-
tion. With 113 years of existence marked
by numerous technological advances di-
rected towards public health issues, the
Butantan Institute is considered one of the
major scientific centers in the world.
In 1900, a commission formed by three
respected physicians and specialists in
public health diseases: Dr. Emı
´lio Ribas,
director of health services for Sa˜o Paulo
State; Dr. Adolpho Lutz, director of the
Bacteriological Institute; and Dr. Vital
Brazil, an assistant of Dr. Lutz at the
same Bacteriological Institute, proposed
the creation of a Serum Therapy Institute
in Sa˜o Paulo to be installed at Fazenda
Butantan, a locality distant from the state
capital at that time. The foundation and
direction of the Serum Therapy Institute
of Sa˜o Paulo State (the current Butantan
Institute) was assigned to Dr. Vital Brazil
Mineiro da Campanha, with the immedi-
ate responsibility of producing a serum to
be used in combating the epidemic of
bubonic plague afflicting the country at
that time [1]. The Institute was officially
established on February 23, 1901, when
Dr. Vital Brazil was designated as its first
director (Figure 1). The first vials of anti-
bubonic-plague serum were produced in
June of that same year, and the Institute
has continued its work over the years in
many different areas, becoming known as
an important producer of several anti-
ophidic serums and a groundbreaking
scientific institute [2]. In parallel, Vital
Brazil worked with snakebite accidents
and studied venom and antibody antive-
nom interactions.
The evolution of the Butantan Institute
can be summarized in four main periods.
The administration of Vital Brazil (1901 to
1927) was accompanied by large invest-
ments in staffing, scientific research, and
the construction of laboratories and an
antiserum factory—in the same international
context as Louis Pasteur’s microbiology
studies and discussions about the specificity
of antivenom antibodies. Based on the
correlation between the severity of the
bite-site inflammation and the snake genus,
Vital Brazil was the first to show that snake
venom ordinarily displayed antigenic spec-
ificity. After reading a report of Calmette’s
anti–Naja tripudians serum [3], he was able
to produce monovalent serums against the
venoms of Bothrops jararaca and Crotalus
durissus terrificus. Vital Brazil also tested
and demonstrated the inefficiency of Calm-
ette’s anti-Naja antiserum for neutralizing
Crotalus or Bothrops toxins [4]. The three
pillars of success of the Butantan Institute
have been preserved and strengthened
since its creation: research, production,
and the popularization of science.
The second phase of the Institute
(1930–1970) was greatly influenced by a
series of authoritarian governments, the
Second World War, the organization of its
pharmacology and pathophysiology labo-
ratories, and the arrival of many foreign
researchers (including Henry Slotta from
the University of Breslau, Germany, who
discovered the female hormone progester-
one and succeeded in isolating crotoxin,
the toxic protein in rattlesnake venom) [5].
The first universities and agencies pro-
moting research in Brazil (National Coun-
cil for Scientific and Technological Devel-
opment [CNPq] and Foundation for
Research Support of the State of Sa˜o
Paulo [FAPESP]) were created in the
1930s. A period of crisis later befell the
Butantan Institute between 1940 and
1960, with a lack of funding and successive
ineffective administrations. The National
Immunization Program, created by the
federal government in 1973, enabled public
producers of serums and vaccines to
organize and modernize their laboratories
and factories, and during the 1980s,
large investments were made in the
Butantan Institute and the Oswaldo
Cruz Foundation (FIOCRUZ) to achieve
self-sufficiency in the production of
vaccines and antibodies against venoms
and toxins. During this period, the
Butantan Foundation was created to
facilitate the management of public
resources, and the Biotechnology Center
was established to develop new vaccines
and serums. Two very successful devel-
opments can be cited for this period: the
development of the hepatitis B vaccine
and the modernization of the production
processes for sera against poisons and
toxins. This period also saw the initiation
of partnerships with the private sector,
including technology transfers for the
production of influenza vaccine at Sanofi
Pasteur. Regulatory frameworks for pub-
lic health were initiated in Brazil starting
in the year 2000, but public laboratories
did not adjust to these legislative man-
dates, and a scarcity of resources (due to
national and international economic crises)
handicapped the leading research and
production institutes, including the Butan-
tan Institute. A major fire in the zoological
collections building in 2010 was a huge loss
to the scientific community.
In 2011, we assumed direction of the
Institute; we then promoted a series of
governance studies and developed a mas-
ter plan for the expansion and profession-
alization of the administration of the
Institute and its Foundation in order to
better coordinate both. Our main goals
were to establish a new organizational
chart for the Institute, enhance public-
private partnerships, and intensify inter-
national exchanges.
Today, the Butantan Institute, linked to
the secretary of health of Sa˜o Paulo State,
has the mission of developing biological
Citation: De Franco M, Kalil J (2014) The Butantan Institute: History and Future Perspectives. PLoS Negl Trop
Dis 8(7): e2862. doi:10.1371/journal.pntd.0002862
Editor: Serap Aksoy, Yale School of Public Health, United States of America
Published July 3, 2014
Copyright: ß2014 De Franco, Kalil. This is an open-access article distributed under the terms of the Creative
Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium,
provided the original author and source are credited.
Funding: The authors have indicated that no funding was received for this work.
Competing Interests: The authors have declared that no competing interests exist.
* Email:
PLOS Neglected Tropical Diseases | 1 July 2014 | Volume 8 | Issue 7 | e2862
products for public health, undertaking
basic and applied research, and promoting
scientific knowledge. The Institute cur-
rently provides 40% of the nationally
produced serums and vaccines that are
distributed without cost to the entire
population of the country by the Brazilian
Health Ministry (Figure 2) through the
Unified Health System (SUS).
World renowned for its studies of
poisonous animals and the venoms and
toxins they produce, the Butantan Institute
has always attracted scientific leaders who,
together with researchers and postgradu-
ate students, develop research projects in
many different areas. Isaias Raw, Antonio
Camargo, Willy Bec¸ak, Ivan Motta, Wil-
mar Dias da Silva, Luiz Trabulsi, and
Maria Siqueria, among others, have
developed projects related to vaccine
production [6–9]; the biology and system-
atic classification of serpents, arthropods,
and parasites; the biochemistry and phar-
macology of venoms and their compo-
nents; the physiopathology of venoms [10–
15]; immunology in response to exposure
to venoms and pathogenic microorgan-
isms; the genetic basis of immune respons-
es; and the cytogenetics and genetics of
poisonous animals [16], and a number of
important reviews have been published in
those fields [17–24].
The Butantan Cultural Development
Center counts among its activities intellec-
tual diffusion and research based on
education, museology, and the history of
science and public health and focuses on
projects promoting scientific discoveries
generated within the Institute, providing
material for consultation in its documen-
tation nucleus and library, and creating
museums and educational programs. The
Cultural Development Center has four
museums—Emilio Ribas, Biological, Mi-
crobiological (Figure 3), and Historical—
and is likewise responsible for coordinating
temporary and itinerant exhibitions that
attract more than 300,000 visitors each
The Research and Production Centers
of the Butantan Institute include 35
scientific laboratories, a Center for Tech-
nological Innovation, a specialized hospi-
tal (Hospital Vital Brazil), three animal
facilities (one each for mammals, spiders,
and serpents), seven vaccine production
centers (including one for veterinary use),
one center for plasma fractioning, and 11
bioproduct manufacturing sites. These
research and production centers employ
approximately 191 researchers, with 420
additional master’s, doctoral, and postdoc-
toral students who undertake scientific
missions within the country and through-
out the world through the auspices of the
World Health Organization (WHO), the
Pan American Health Organization
(PAHO), the United Nations Children’s
Fund (UNICEF), and the United Nations
(UN) (Figure 4). Fully focused on the
development of scientific research and the
production of immunobiologicals used in
public health campaigns, the Butantan
Institute produces publications available
for unrestricted consultation in all of its
areas of action and offers internships as
well as extension and postgraduate courses
(MS, PhD, and MBA).The Butantan
Institute has two PhD courses: Toxinology
and Biotechnology (the latter offered in
association with the University of Sa˜o
Figure 1. The Butantan Institute was founded in 1901, with Vital Brazil as its first
Figure 2. The Butantan Institute is one of the main public producers of serums and
vaccines in Brazil. Abbreviations: Bi, billion; FAP, Fundac¸a
˜o Ataulfo de Paiva; FUNED,
Ezequiel Dias Foundation; MM, millions; MOH, Ministry of Health; OPAS, Organizac¸a
Panamericana de Sau
´de; TECPAR, Institute of Technology of Parana
PLOS Neglected Tropical Diseases | 2 July 2014 | Volume 8 | Issue 7 | e2862
The productive complex of the Institute
has dominated the technologies required
for producing at least 12 types of serums
and seven vaccines (Figure 5) utilized by
the Brazilian Health Ministry [25] and has
been working with technology transfer
from public and private producers in
industrialized countries as well as on its
own independent production innovation
and the development of technologies for
vaccine production.
Technology transfer is a complex,
multifaceted, and delicate process that
involves not only transferring basic knowl-
edge but also techniques for quality
control and quality guarantees, the dom-
ination of regulatory processes, clinical
studies to guarantee the adequacy of the
products, and the capacity to adapt to
local conditions, all done while renovating
and updating production facilities to
international quality standards. The Bu-
tantan Institute industrial complex was
installed in 1998 and inaugurated in 2007;
it is capable of producing vaccines against
various influenza virus subtypes, such as
H1N1, swine flu, H5N1, and avian flu.
Just four years later in 2011, the Institute
delivered the first lot of vaccines against
influenza entirely produced in Brazil and
received a certificate of good production
practices from the Brazilian National
Agency of Public Health (ANVISA) in
2012. This was the first successful techno-
logical transfer completed in Brazil be-
tween Sanofi-Pasteur and the Butantan
Institute [26]. Three new agreements were
recently signed between international lab-
oratories and the Butantan Institute for the
development and production of vaccines
against human papillomavirus (HPV) and
hepatitis A with Merck Sharp & Dohme
(MSD) and against acellular pertussis with
GlaxoSmithKline (GSK) through technol-
ogy transfer.
Additionally, the Butantan Institute
independently produced a trivalent vac-
cine against diphtheria, tetanus, and
pertussis (whooping cough) as well as a
vaccine against hepatitis B in the 1980s
A number of international agencies
have demonstrated interest in Brazil in
terms of producing and furnishing vac-
cines, with demand from Colombia and
some African countries for technology
transfers and collaboration agreements to
produce Butantan antiserums. Additional-
ly, researchers from the Butantan Institute
are working through grants provided by
financing agencies (FAPESP, Coordina-
tion for the Improvement of Higher
Education Personnel (CAPES), CNPq,
the Brazilian Development Bank
(BNDES), and the Fulbright Foundation)
on various projects in cooperation with
scientists from various international insti-
tutions [27].
The technical competency of the Bu-
tantan Institute and its investments in
upgrading its production facilities to both
national and international standards (the
Food and Drug Administration [FDA],
WHO, and ANVISA) has stimulated
interest in partnerships with international
universities and other institutes dedicated
to public health. Examples of these
partnerships and developing projects in-
clude collaboration with the National
Institute of Health (NIH), for the production
of vaccines against rotavirus and the dengue
virus; the Boston Children’s Hospital at the
Harvard Medical School, for developing a
vaccine against pneumococcus; the Sabin
Figure 3. The Butantan Institute Cultural Center—Microbiology Museum.
PLOS Neglected Tropical Diseases | 3 July 2014 | Volume 8 | Issue 7 | e2862
Institute and George Washington Universi-
ty, for developing a vaccine against schisto-
somiasis (the parasites Necator and Schistoso-
ma); and the Infectious Diseases Research
Institute in Seattle and the University of
Washington, for developing a vaccine
against canine leishmaniasis.
The prestige of the Butantan Institute in
the area of toxins produced by animals
and microorganisms was decisive in its
hosting of one of the Centers for Research,
Innovation and Diffusion supported by
FAPESP since 2002—the Center of Ap-
plied Toxinology. This program was
developed to fund institutions with proven
capacity in attaining world-class research
levels. The initial program was quite
successful, and FAPESP approved a new
challenge in 2013—the Center for Re-
search in Toxins, Immune Responses, and
Cellular Signaling—that would concentrate
on studies concerning the biochemical,
molecular, and cellular action mecha-
nisms of toxins demonstrating therapeu-
tic potential, with the objective of
establishing proof of concept based on
the analyses of molecular signaling net-
works. Strategic planning calls for the
results of these research projects to be
transferred to industry through processes
mediated by the Technology Innovation
Office of the Butantan Institute.
The Butantan Institute is currently pro-
posing the creation of the Butantan Institute
for Biotechnological Innovation (IIBB) to
use its accumulated technical-scientific
experience in an institutional manage-
ment system designed to promote agility
in the administration of innovation. An
international committee composed of
renowned scientists is currently being
formed that will analyze all of the
research lines of the Institute and, togeth-
er with the directory, propose a strategic
plan for the next ten years and reorganize
all of the research groups in the IIBB that
are involved in research and develop-
ment. This is one of the Institute’s most
important programs for the future, as it is
designed to promote interactions with
private partners for the development of
its discoveries and innovations and the
incorporation of new products into ac-
tions directed toward public health. This
Figure 4. Scientific research and development laboratory at the Butantan Institute.
PLOS Neglected Tropical Diseases | 4 July 2014 | Volume 8 | Issue 7 | e2862
program proposes a new juridical model
(special autarchy) for the Institute, de-
signed to achieve autonomous adminis-
trative governance, combining Institute
and Foundation to promote scientific
research, technological development, and
the production of vaccines and immuno-
biologicals in Brazil.
Our greatest efforts will always be
directed towards maintaining the highest
levels of excellence in research, develop-
ment, and the production of vaccines and
serums and guaranteeing the position of
the Butantan Institute as a bridge between
research and production so that Brazil will
stay at the forefront of progress in public
health considerations.
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... The Butantan Institute, a leader in contributing to studies in Brazil, is an institution that was born in 1901 in the state of São Paulo with to produce serum against bubonic plague [57]. Over the years, the institute has become one of the main scientific institutions in Brazil, known worldwide for studying the toxins of venomous animals, in addition to projects related to vaccines production, which attracted the attention of several international institutions for establishment of partnerships [57]. ...
... The Butantan Institute, a leader in contributing to studies in Brazil, is an institution that was born in 1901 in the state of São Paulo with to produce serum against bubonic plague [57]. Over the years, the institute has become one of the main scientific institutions in Brazil, known worldwide for studying the toxins of venomous animals, in addition to projects related to vaccines production, which attracted the attention of several international institutions for establishment of partnerships [57]. In relation to snakes, from the research carried out by the institution, various serums are produced, such as antibotropic, anticrotalic and antielapidic, which are made available to the population free of charge through the Health Ministry (see the Institute's website). ...
Full-text available
The peptides present in snake venoms are studied because of their properties, constitutions, mechanisms of action and pharmacological potential. Recognizing this potential, the present study reports the contributions of Brazilian researchers about snake peptides, between 1975 and July 2020. Thus, this study serves as a basis for monitoring this theme in Brazil, referring to the trends and patterns of scientific production. The results indicated a significant increase in Brazilian scientific production over the years, highlighting institutions located in São Paulo state as, the Butantan Institute and University of São Paulo. The main journal where Brazilian authors publish their research is the Toxicon Journal. Collaborative networks were identified between Brazilian institutions and among other countries with Brazil. The most investigated species are found in brazilian territory, mainly those belonging to the genus Bothrops and the species Crotalus durissus. The increase in studies about this theme in Brazil is evident, however, a gap is highlighted for states outside the southeastern region and for other venomous species.
... Antivenom therapy is the only effective treatment for snake envenomation and Instituto Butantan is the main Brazilian producer of the antivenom by the immunization of horses with selected venoms (Franco and Kalil, 2014). The Laboratory of Herpetology keeps a variety of snake species to milk and prepare the venoms for antivenom production, in addition to scientific research for venom compositional and functional understanding and improvement of the antivenom therapy (Grego et al., 2021). ...
This work compared the presence of phospholipase A2 inhibitors (PLIs) in the serum of 19 snake species maintained at Instituto Butantan to better understand the mechanisms of venom resistance in snakes and improve the treatment of snakebite. PLI was isolated from blood of 19 snake species by one-step chromatography and identified in all samples, besides its identity was confirmed through the interaction with both phospholipase A2 and anti-γPLI. These findings highlight the diversity of snake serum PLIs and emphasize the importance of structure-function studies.
... The former is linked to the Secretary of Health of the State of São Paulo, Brazil, while the latter belongs to the University of Costa Rica, hence both being public institutions. IB and ICP play a leading role in the region, not only in scientific and technological research, but also in antivenom development and production, and in the promotion of regional efforts to confront snakebite envenomings (Gutiérrez and Rojas, 1999;de Franco and Kalil, 2014). Interestingly, since the first decades of the 20th century, collaborative links were established between Brazil and Costa Rica in this field. ...
Instituto Butantan (São Paulo, Brazil) and Instituto Clodomiro Picado (San José, Costa Rica) are public institutions devoted to scientific and technological research, production of antivenoms and other immunobiologicals, and a variety of public health interventions aimed at confronting the problem of snakebite envenoming in their countries and elsewhere. In the context of the 120th anniversary of Instituto Butantan, this work describes the historical developments in the relationship between these institutions, which has evolved into a solid cooperation platform in science, technology, and public health. The relationship between Instituto Butantan and Costa Rica started early in the 20th century, with the provision of Brazilian antivenoms to Costa Rica through the coordination of Instituto Butantan and the health system of Costa Rica, with the leadership of Clodomiro Picado Twight. After the decade of 1980, a prolific collaborative network has been established between Instituto Butantan and Instituto Clodomiro Picado (founded in 1970) in the areas of scientific and technological research in pharmacology, biochemistry, experimental pathology, immunology, and public health, as well as in antivenom development, production, preclinical evaluation, and quality control. In addition, both institutions have played a key role in the integration of regional efforts in Latin America to create a network of public institutions devoted to antivenom production and quality control, in close coordination with the Pan American Health Organization (PAHO). This long-standing partnership is an example of a highly productive south-south cooperation under a frame of solidarity and public well-being.
... Butantan Institute received the certificate of current good manufacturing practices (cGMP) from the Brazilian Regulatory Agency (ANVISA) and delivered the first lot of egg-based seasonal trivalent split influenza vaccine entirely produced in Brazil for the 2013 campaign. This was the first successful technological transfer completed in Brazil between Sanofi-Pasteur and the Butantan Institute [27][28]. For the 2019 vaccination campaign, Butantan Institute produced and delivered 59 million doses of trivalent seasonal influenza for the Brazilian Ministry of Health, representing 92% of the total demand (64 million doses), with the remaining doses supplied by Sanofi-Pasteur (Fig 1). ...
Full-text available
Increasing pandemic influenza vaccine manufacturing capacity is considered strategic by WHO. Adjuvant use is key in this strategy in order to spare the vaccine doses and by increasing immune protection. We describe here the production and stability studies of a squalene based oil-in-water emulsion, adjuvant IB160, and the immune response of the H7N9 vaccine combined with IB160. To qualify the production of IB160 we produced 10 consistency lots of IB160 and the average results were: pH 6.4±0.05; squalene 48.8±.0.03 mg/ml; osmolality 47.6±6.9 mmol/kg; Z-average 157±2 nm, with polydispersity index (PDI) of 0.085±0.024 and endotoxin levels <0.5 EU/mL. The emulsion particle size was stable for at least six months at 25°C and 24 months at 4–8°C. Two doses of H7N9 vaccine formulated at 7.5 μg/dose or 15 μg/dose with adjuvant IB160 showed a significant increase of hemagglutination inhibition (HAI) titers in sera of immunized BALB/c mice when compared to control sera from animals immunized with the H7N9 antigens without adjuvant. Thus the antigen-sparing capacity of IB160 can potentially increase the production of the H7N9 pandemic vaccine and represents an important achievement for preparedness against pandemic influenza and a successful North (IDRI) to South (Butantan Institute) technology transfer for the production of the adjuvant emulsion IB160.
Full-text available
O desenvolvimento e a capacidade de produção de vacinas são fundamentais no enfrentamento de doenças. Esse processo torna-se urgente em pandemias, como a da Covid-19, cujo número de mortes é elevadíssimo. Este estudo pretende indicar como o uso da estratégia de transferência de tecnologia no Brasil, pelo Instituto Butantan, beneficia o desenvolvimento de vacinas. Utilizando pesquisa documental, são abordados os desafios enfrentados. A estrutura já instalada no Butantan foi imprescindível para o seu protagonismo no enfrentamento da Covid-19, bem como a realização de parcerias e a utilização dos conhecimentos já adquiridos. O uso de tecnologias já dominadas acelera o processo de desenvolvimento, reduz o investimento financeiro e permite a produção integralmente nacional, contribuindo para reverter sua situação de vulnerabilidade tecnológica. Para que essas iniciativas tenham continuidade, é essencial uma política para investimentos no complexo industrial da saúde e apoio a projetos e pessoal envolvido em PD&I na instituição e no Brasil.
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This book, "Vaccines and Immunization in Brazil: horizons for the next 20 years", discusses from foresight and sustainability perspectives, scenarios for the declining vaccine coverage in the country, a major issue now in COVID-19 pandemic, and for the very low investment in vaccine innovation, technological development and production in the country. The major regulatory, biosafety and bioethical issues are discussed. The main conclusion of the book is that a new National Vaccine Plan is necessary but will be insufficient if not complemented by a long-term and sustainable National Strategic RD&I Vaccine Plan up to 2050, which will be crucial for implementation of a CEPI-like model in Brazil (CEPI- Coalition for Epidemic Preparedness and Innovation), providing adequate institutional and financial support for emerging diseases and pandemics vaccine preparedness.
Natural history collections (NHCs) are important resources for a diverse array of scientific fields. Recent digitization initiatives have broadened the user base of NHCs, and new technological innovations are using materials generated from collections to address novel scientific questions. Simultaneously, NHCs are increasingly imperiled by reductions in funding and resources. Ensuring that NHCs continue to serve as a valuable resource for future generations will require the scientific community to increase their contribution to and acknowledgement of collections. We provide recommendations and guidelines for scientists to support NHCs, focusing particularly on new users that may be unfamiliar with collections. We hope that this perspective will motivate debate on the future of NHCs and the role of the scientific community in maintaining and improving biological collections.
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Streptococcus pneumoniae remains an important cause of disease with high mortality and morbidity, especially in children and in the elderly. The widespread use of the polysaccharide conjugate vaccines in some countries has led to a significant decrease in invasive disease caused by vaccine serotypes, but an increase in disease caused by non-vaccine serotypes has impacted on the overall efficacy of these vaccines on pneumococcal disease. The obvious solution to overcome such shortcomings would be the development of new formulations that provide serotype-independent immunity. This review focuses on the most promising approaches, including protein antigens, whole cell pneumococcal vaccines, and recombinant bacteria expressing pneumococcal antigens. The protective capacity of these vaccine candidates against the different stages of pneumococcal infection, including colonization, mucosal disease, and invasive disease in animal models is reviewed. Some of the human trials that have already been performed or that are currently ongoing are presented. Finally, the feasibility and the possible shortcomings of these candidates in relation to an ideal vaccine against pneumococcal infections are discussed.
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Brasil). Dynamis Fecha de recepción: 2 de febrero de 2010 [0211-9536] 2011; 31 (1): 65-83 Fecha de aceptación: 4 de enero de 2011 SUMARIO: 1.—Introducción. 2.—La peste se aproxima a Brasil. 3.—El puerto de Santos. 4.—La peste llega a Brasil. 5.—Las investigaciones de los representantes de DGSP. 6.—La peste en Sao Paulo. 7.—Comentarios finales. RESUMEN: En octubre de 1899, la peste bubónica llegó a Brasil, por el puerto de Santos. Ciudad paulista de intenso flujo portuario fue la puerta de entrada de la epidemia de peste que asoló varias ciudades brasileñas a comienzos del siglo XX. Esta epidemia fue propulsora de una acción conjunta de varios estados para combatirla y, más que eso, ante las dificultades de importa-ción de suero preparado en Europa, llevó a la creación, en 1899, del Instituto Butantan en Sao Paulo, y, en 1900, del Instituto Soroterápico Municipal, en Río de Janeiro. Ambas instituciones fomentaron la elaboración de sueros y vacunas contra la peste estableciendo un patrón de estos productos según las condiciones del país. Las medidas de salud pública desarrolladas hasta entonces se habían aplicado de forma aislada y puntual en Brasil. El doctor Oswaldo Cruz, tras tres años de especialización en el Instituto Pasteur de Paris trabajó en la identificación de la peste en Santos, juntamente con los científicos Adolfo Lutz y Vital Brazil. Este artículo pretende analizar la llegada de la epidemia de peste bubónica al estado de Sao Paulo y las acciones llevadas a cabo en el campo de la salud pública para combate de la enfermedad y la asistencia a los enfermos, especialmente en los primeros años del siglo XX. Las fuentes principales para este análisis son los periódicos paulistas, concretamente O Estado de São Paulo, los informes del Ministerio de Justicia y los mensajes elaborados por el presidente del estado de Sao Paulo.
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Adhesins need to be exposed on the surface of pathogenic bacteria to properly interact with host tissues and allow establishment of the infection. This fact implies that, in theory, one could manage or avoid infection by controlling adhesins' function, and also by indirectly detecting bacteria through their surface-exposed adhesins. Besides, binding of anti-adhesin immunoglobulins on the bacterial surface tend to promote the opsonization of the pathogen. Therefore, bacterial adhesins represent a great target to develop new biopharmaceuticals, which may become commercially and medically important products. In this review, we will summarize the biological importance of bacterial adhesins, and also discuss some recent patents related to these molecules, as well as their use and possible new future developments in this area.
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these institutions maintained scientific research programs but had limited capability for meeting good manufacturing practices (GMPs) in vaccine production. The implementation of the MH policy of local procurement required substantial investments to upgrade the production capabilities of these institutes.
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This review summarizes the key contributions to our knowledge regarding the immune response induced by snake venom toxins, focusing particularly on the production of antibodies and their venom-neutralizing effects. We cover the past and present state of the art of anti-snake venom production, followed by an overview of the venomous snakes and their venoms. The toxic properties of relevant snake venom toxins are approached in some details, with particular emphasis on the molecular domains responsible for binding to cells or plasma components in victims. The interactions of these domains are also reviewed, particularly the putatively relevant epitopes, along with the immune system and the resulting antibodies. We also review trials aimed at reducing the quantities of non-relevant antibodies in the antivenoms by substituting whole venoms with purified toxins to immunize animals, or the immunogenicity of the heterologous antivenom antibodies by humanizing their molecules.
The conference was a true forum for the Emerging Markets global vaccine community. Close to 100 senior-level representatives from large and small vaccine-related private sector firms, from the UN system (World Health Organization -WHO and Pan American Health Organization -PAHO) as well as donors (The Global Alliance for Vaccines and Immunization -GAVI and the Gates Foundation), convened in Berlin in an atmosphere of open and helpful information exchange. The great challenges involved in working in Emerging Markets were discussed; the speakers repeatedly highlighted cultural awareness and close communication as key elements for success. Nonetheless an underlying optimism and can-do attitude permeated the discussions: many among the audience are directly responsible for the historically unprecedented success in vaccine delivery to third world countries occurring over the last decade. : Chairing this plenary session was by Dr. Jon Kim Andrus, Pan American Health Organization's (PAHO) Deputy Director. He is a public health expert with over 25 years work experience in vaccines, immunization, and primary care in developing countries. The panelists were Dr. Jorge Kalil, President of the Butantan Institute, in Sao Paulo, Brazil and Lic. Abel Di Gilio, President of Sinergium Biotech, in Buenos Aires, Argentina. Both speakers have extensive experience in the building of vaccine production factories in emerging market countries, and most importantly, in building, promoting and securing, at the national and international levels, the institutional and political support necessary for sustainability and growth.
In 1923 Karl H. Slotta obtained his PhD in chemistry from the University of Breslau, Germany, where he continued to work. At the instigation of the gynaecologist Ludwig Fraenkel, Slotta made the first isolation of progesterone in 1933. In 1934 he proposed the correct structural formula. Slotta was appointed professor of chemistry in 1935, but with the oppression of the Nazi regime mounting, he soon left Germany with his family to take a post at the Instituto Butantan, Brazil. Initially he worked on the chemistry of coffee. In 1938 Slotta and his brother-in-law Heinz Fraenkel-Conrat isolated crotoxin from Crotalus durissus terrificus venom, the first snake toxin to be obtained in crystalline form. They had evidence to suggest that the toxicity of crotoxin was due to a phospholipolytic action on nerve lipids. In 1938 Slotta's department was closed; he subsequently co-founded a biopharmaceutical company. In 1956 Slotta was appointed research professor of biochemistry at the University of Miami, USA. Slotta purified the most basic polypeptide from Naja naja venom, known as direct lytic factor, and with James Vick identified this as cardiotoxin. Karl H. Slotta will be remembered not only for his skill as a biochemist but also for his indomitable and cheerful spirit.
It has long been recognized that snake venom serine proteinases (SVSPs) affect various physiological functions including blood coagulation, fibrinolysis, blood pressure and platelet aggregation. Therefore, SVSPs have been used as refined tools to study molecular mechanisms involved in the activation of key factors that control hemostasis and as therapeutic agents in various thrombotic and hemostatic conditions. The aim of this review is to highlight the state of our knowledge on the advances made in SVSP research since the 18th century. It includes the personal accounts of some distinguished scientists that addressed specific problems and contributed to advance the field.
In October 1899, the bubonic plague arrived in Brazil through the port of Santos. A city of intensive port activity, Santos was the gateway for a plague epidemic that devastated several cities in Brazil in the early 20th century and prompted joint action by several states to fight it. More importantly, given the difficulties and delays in importing anti-plague serum from Europe, it led to the creation of the Butantan Institute in Sao Paulo (in 1899) and the Municipal Serotherapeutic Institute in Rio de Janeiro (in 1900), which developed and standardized anti-plague serum and vaccines according to the particular conditions of the country. Until then, public health efforts had been isolated and had not reached the whole country. Oswaldo Cruz, newly arrived after three years of specialization at the Pasteur Institute in Paris, worked with scientists Adolfo Lutz and Vital Brazil on identifying the plague in Santos. This article analyzes the arrival of the bubonic plague epidemic in the state of Sao Paulo and the public health measures taken to combat the disease and provide patient care in the early part of the 20th century. The primary sources for this analysis were the São Paulo newspapers, especially O Estado de Sao Paulo, and reports from the Ministry of Justice and the President of the State of Sao Paulo.
The identification of novel endogenous and exogenous molecules acting in the complex mechanism of regulating the vascular tonus has always been of great interest. The discovery of bradykinin (1949) and the bradykinin-potentiating peptides (1965) had a pivotal influence in the field, respectively, in understanding cardiovascular pathophysiology and in the development of captopril, the first active-site directed inhibitor of angiotensin-converting enzyme, and used worldwide to treat human hypertension. Both discoveries originated from studies of envenoming by the snake Bothrops jararaca. The aim of the present article is to reveal that the snake proline-rich oligopeptides, known as bradykinin-potentiating peptides, are still a source of surprising scientific discoveries, some of them useful not only to reveal potential new targets but also to introduce prospective lead molecules for drug development. In particular, we emphasize argininosuccinate synthetase as a new functional target for one of bradykinin-potentiating peptides found in B. jararaca, Bj-BPP-10c. This decapeptide leads to argininosuccinate synthetase activation, consequently sustaining increased nitric oxide production, a critical endogenous molecule to reduce the arterial blood pressure.