products under development

 

 Editor de Conteúdo ‭[1]‬

 
vaccines

 

dengue

Butantan developed the dengue vaccine production in partnership with the United States National Institutes of Health (NIH). The vaccine viruses were obtained through deletion of viral gene segments. The tetravalent vaccine, made up of genetically engineered attenuated viruses, should protect against the four types of dengue virus. Production expectations are of nearly 100 million doses per year. This project is sponsored by the Brazilian Development Bank (BNDES).

The second phase of the clinical trials began in August 2014 and the expectation is to vaccinate another 250 volunteers who have or have not had previous exposure to the dengue virus.

The studies are being carried out in partnership with the University of São Paulo Medical School and the clinical trial participants, adults aged 18-59 years, are treated at the Instituto Central Clinical Research Center and at Clinicas de São Paulo Children's Institute.

The participants will be monitored over a five-year period, which is enough time to annually check the vaccine's immune response and the protection it provides.

 

rotavirus

In partnership with the United States National Institutes of Health (NIH), Butantan developed the production of the pentavalent rotavirus vaccine. This oral vaccine is made up of five strains of genetically rearranged and attenuated human and bovine rotavirus. The new vaccine aims at including the most commonly found genotypes in Brazil and will contribute to diminishing the incidence of hospitalizations and deaths from rotavirus, especially in children under the age of five.  Moreover, the vaccine will cost less and cover more than the one currently being used, as it will be made with domestic technology and the current vaccine is monovalent.

 

pneumococcus

The current vaccines against pneumococus are based on conjugated polysaccharides and show variable coverage, high cost and can lead to serotype substitution. In partnership with Harvard's Boston Children' s Hospital, Butantan developed a cellular vaccine that induces independent protection of polysaccharides, allowing a universal vaccination with low production costs. A pilot study of the scaled production process was developed in compliance with the Good Manufacturing Practices (Boas Práticas de Fabricação, BPF). This vaccine is in phase 1 of a clinical trial in the United States. The project is backed the Bill Gates Foundation/PATH (Program for Appropriate Technology in Health).

Other vaccine strategies being developed are based on conserved and/or immunogenic pneumococcus surface proteins, conjugated, or not, to few polysaccharides of greater prevalence, and combined with the use of strong adjuvants like MPLA or even with whole-cell pertussis vaccine. 

 

DTPlow

Instituto Butantan developed an innovation in the production of whole-cell pertussis vaccine (Plow) that reduces the lipopolysaccharide (LPS) content, which is the component responsible for the fever and inflammatory reactions of the diphtheria, tetanus and pertussis (DTP) vaccine adsorbed. The chemical extraction of the LPS resulted in a significant reduction of reactogenicity, had no variance in the vaccine potency and did not add significant costs with respect to the traditional vaccine. This new process allows the recovery of LPS, which is transformed into monophosphoryl lipid A (MPLA), a powerful vaccine adjuvant. As such, the production cost is shared between two products, whole-cell pertussis vaccine (Plow) and MPLA.


heptavalent vaccine

The heptavalent vaccine project aims at the technological development and the production of the combined heptavalent vaccine (diphtheria, tetanus, pertussis, hepatitis B (recombinant), Haemophilus influenza and type b (Hib) conjugate, Meningococcal group C-CRM197 conjugate vaccine and inactivated polio) for the Ministry of Health’s National Immunization Program. The heptavalent vaccine will be developed in collaboration with Instituto Butantan (IB) laboratories, FIOCRUZ/Bio-Manguinhos and Funed. This vaccine will reduce the number of injections and the administration costs, which will also diminish visits to health centers, facilitating and increasing vaccine coverage throughout Brazil. We highlight the project's originality, as there is no similar vaccine available anywhere in the world market.

 

Recombinant BCG expressing Pertussis - neonatal vaccine against whooping cough

The current vaccines against whooping cough, or pertussis, are not administered to children younger than 6 months of age, which means that this disease causes mortality in this age group. A recombinant BCG vaccine (Bacillus Calmette-Guerin) that produces a genetically detoxified pertussis subunit was produced. Like BCG, this vaccine can be given at birth. When injected in newborn mice, the vaccine was able to confer 100% protection against lethal infection by Bordetella pertussis. This vaccine is being prepared in compliance with the Good Manufacturing Practices (Boas Práticas de Fabricação, BPF) for implementing phase 1 clinical trials. This project receives support from BNDES.

 

Recombinant Onco BCG- Treatment of bladder cancer

The BCG strain is not only used as a vaccine against tuberculosis, but also as an immunotherapy for the treatment of bladder papilloma, which in most cases prevents the need for surgery and/or chemotherapy. Treatment with BCG is thought to trigger an immune response that prevents or delays the tumor from resurging. Studies of a bladder tumor in an animal model demonstrated that the recombinant onco BCG Pertussis strain sets in motion a modified immune response and suggests that the recombinant BCG would be more effective for the treatment of tumors. This strain is being prepared as an immunotherapy formulation that complies with the Good Manufacturing Practices (Boas Práticas de Fabricação, BPF) for implementing phase 1 clinical trials. This project receives support from BNDES.


 

other products

 

Monophosphoryl lipid A (BpMPLA) - a Powerful Immunological Adjuvant

Instituto Butantan developed Monophosphoryl lipid A (BpMPLA), obtained from the LPS of Bordetella pertussis, as a by-product in the production of the new pertussis vaccine (Plow) that has potential for large-scale production. The BpMPLA adjuvant has been tested with the influenza vaccine and has been shown to be a powerful adjuvant that allows a fourfold reduction of the influenza vaccine dosage, thus increasing production capacity and reducing costs. Experimental studies of BpMPLA with hepatitis B vaccine adsorbed (recombinant) produced by Instituto Butantan showed anti-HBsAg quantities similar to those of the traditional vaccine, only using half of the vaccine antigen concentration, thus allowing the increased production of this vaccine. Furthermore, the adjuvant can be used for the development of new vaccines. BpMPLA is being tested with canine visceral leishmaniasis vaccine through an agreement with IDRI (Infectious Disease Research Institute - Seattle).

 

haemophilus - a new method of for conjugate vaccine

a new conjugate methodology was developed for the production of the haemophilus vaccine. This methodology presents a greater chemical yield, thus allowing to diminish production costs. This process has been patented. Currently, the capsular polysaccharide production process of Haemophilus influenzae type b and its conjugate is in the scaling phase. This project receives support from BNDES.​


pulmonary surfactant

Butantan, through a private sector partnership, developed a pig-derived pulmonary surfactant that can be used in the treatment of low birth-weight infant respiratory distress syndrome. The product should make a significant contribution to the reduction of premature infant mortality once it is available at all Brazilian public maternity wards at a significantly reduced cost.

 

Hemoderivatives

A process for separating human plasma by using a modern protein purification methodology allows the achievement of a high quality, yield and purity. The process will also facilitate the research on new biopharmaceuticals based on the same material, plasma. At first, the separation plant will produce immunoglobulin for intravenous use (IGIV). Making domestically produced IGIV available in Brazil will be a landmark development and Butantan hopes to contribute to it. Other products, such as factor VIII, factor IX, prothrombin complex and albumen will also have to be isolated.

 

adjuvants

Research performed at Instituto Butantan has been advancing in the realm of vaccine adjuvants, aiming at using smaller doses of vaccines and amplifying the organism's responses against disease-causing microorganisms. Two new adjuvants have been shown to be promising:

• Monophosphoryl Lipid A (MPLA) - used as a H1N1 virus vaccine adjuvant, clinical trials showed that it is safe to use and that it maintains the same level of the vaccine’s effectiveness, but only 1/4 of the dosage. 

• Unstructured porous silica (SBA-15) - seems promising as an adjuvant or oral vaccine vehicle since it has an extremely organized structure that enables interaction with atoms, ions and molecules, not only on its surface, but also in its interior.  The Immunochemistry Laboratory identified SBA-15 as a vaccine adjuvant. Preliminary tests have been carried out with the hepatitis B vaccine in mice. In the event that the human trials be confirmed, the expansion of oral vaccine use will allow greater economic savings and safety, eliminating the need for needles and syringes, increasing the number of people immunized and allowing the application of smaller doses than those currently used. Development of this project is a partnership between Butantan and the Cristália Laboratory.


anti-apian serum

anti-apian serum is being developed for the treatment of ​accidents with bees, Apis mellifera.​

 

 Editor de Conteúdo ‭[2]‬