1.The Importance of Animal Models in Tuberculosis Vaccine Development
Armando Acosta ; Mohd Nor Norazmi ; Rogelio Hernandez- Pando ; Nadine Alvarez ; Reinier Borrero ; Juan F Infannfante ; Maria E Sarmiento
Malaysian Journal of Medical Sciences 2011;18(4):5-12
Research, development, and production of vaccines are still highly dependent on the use of animal models in the various evaluation steps. Despite this fact, there are strong interests and ongoing efforts to reduce the use of animals in vaccine development. Tuberculosis vaccine development is one important example of the complexities involved in the use of animal models for the production of new vaccines. This review summarises some of the general aspects related with the use of animals in vaccine research and production, as well as achievements and challenges towards the rational use of animals, particularly in the case of tuberculosis vaccine development.
2.Identification of Dengue-specific B-Cell Epitopes by Phage-display Random Peptide Library
Nevis Amin ; Alicia Aguilar ; Frank Chamac ho ; Yaime Vázquez ; Maritza Pupo ; Juan Carlos Ramirez ; Luis Izquierdo ; Felix Dafhnis ; David Ian Stott ; Ela Maria Perez ; Armando Acosta
Malaysian Journal of Medical Sciences 2009;16(4):4-14
Background: Dengue is the most important human viral disease transmitted by arthropod
vectors. The availability of random peptide libraries (RPL) displayed on phage has provided a powerful
tool for selecting sequences that mimic epitopes from microorganisms that are useful for diagnostic
and vaccine development purposes. In this paper, we describe peptides that resemble the antigenic
structure of B-cell epitopes of dengue virus identified from a phage-peptide library using human sera
containing polyclonal antibodies against dengue virus.
Materials and Methods: Eighteen phage clones were isolated from the phage-display peptide
library, J404, by affinity selection using human antisera against dengue virus type 3. These clones were
tested for reactivity by ELISA with a panel of hyperimmune ascitic fluids (HAFs) containing antibodies
either against all four dengue serotypes, West Nile virus (WNV) or Eastern equine encephalitis virus
(EEEV) with control ascitic fluid (NAF) used as a negative control.
Results: Eight clones were recognized by HAFs against the four dengue serotypes, of which
four significantly inhibited binding of anti-dengue antibodies to the virus. Two peptides with similar
sequences to regions of NS3 and NS4B non-structural dengue virus proteins were identified.
Conclusion: Our results suggest that these peptides could be used for the development of
diagnostic tools for the detection of dengue virus infection and for a potential vaccine against this
pathogen.
3.Histopathological Study of the Lungs of Mice Receiving Human Secretory IgA and Challenged with Mycobacterium tuberculosis
Nadine Alvarez ; Juan Francisco Infante ; Reinier Borrero ; Dulce Mata ; Jorge BarriIos-Payan ; Md. Murad Hossain ; Norazmi Mohd Nor ; María Elena SarmiIento ; Rogelio Hernandez-Pando ; Armando Acosta
Malaysian Journal of Medical Sciences 2014;21(3):31-37
Background: Humoral and cellular immune responses are associated with protection against extracellular and intracellular pathogens, respectively. In the present study, we evaluated the effect of receiving human secretory immunoglobulin A (hsIgA) on the histopathology of the lungs of mice challenged with virulent Mycobacterium tuberculosis.
Methods: The hsIgA was purified from human colostrum and administered to Balb/c mice by the intranasal route prior to infection with M. tuberculosis or in a pre-incubated formulation with mycobacteria, with the principal aim to study its effect on qualitative pulmonary histopathology.
Results: The intranasal administration of hsIgA and the pre-incubation of mycobacteria with this preparation was associated with the presence of organised granulomas with signs of immune activation and histological features related to efficient disease control. This effect was highly evident during the late stage of infection (60 days), as demonstrated by numerous organised granulomas with numerous activated macrophages in the lungs of treated mice.
Conclusion: The administration of hsIgA to mice before intratracheal infection with M. tuberculosis or the pre-incubation of the bacteria with the antibody formulation induced the formation of well-organised granulomas and inflammatory lesions in lungs compared with non-treated animals which correlates with the protective effect already demonstrated by these antibody formulations.
4. Specific and cross-reactive immune response against Mycobacterium tuberculosis antigens in mice immunized with proteoliposomes from Mycobacterium bovis BCG
Nadine ALVAREZ ; Daymí SERPA ; Yanely TIRADO ; Reinier BORRERO ; Sonsire FERNÁNDEZ ; Rubén CABRERA ; Yolanda VALDES ; Caridad ZAYAS ; Reinaldo ACEVEDO ; Luis IZQUIERDO ; José Luis PÉREZ ; Ramlah KADIR ; María Elena SARMIENTO ; Mohd-Nor NORAZMI ; Mohd-Nor NORAZMI ; Armando ACOSTA
Asian Pacific Journal of Tropical Biomedicine 2017;7(3):188-192
Objective To characterize the immunogenicity and the induction of cross-reactive responses against Mycobacterium tuberculosis (M. tuberculosis) of a proteoliposome (PL) from Mycobacterium bovis Bacillus Calmette–Guérin (BCG) with and without alum hydroxide (AL) as adjuvant (PLBCG-AL and PLBCG, respectively) in BALB/c mice. Methods BALB/c mice were inoculated with phosphate buffer solution, BCG, PLBCG and PLBCG-AL. The humoral immunogenicity was determined by ELISA [immunoglobulin G (IgG), IgG1 and IgG2a] and the cellular immunogenicity was evaluated in vivo by delayed type hypersensitivity. The humoral cross-reactive response against M. tuberculosis was determined by Western blot. Results Sera from animals immunized with PLBCG-AL and PLBCG showed significant increase in specific total IgG and IgG1 antibodies and the presence of cross-reactive antibodies against M. tuberculosis antigens, which were more intense with the use of alum as adjuvant. Mice immunized with PLBCG and PLBCG-AL also showed a specific cellular response in vivo. Conclusions The cellular and humoral immunogenicity of PLBCG and the capacity to induce cross-reactive responses against M. tuberculosis is in agreement with the protective capacity previously demonstrated by this vaccine candidate and supports the continuation of its evaluation in further stages.
5. Liposomes as immunological adjuvants and delivery systems in the development of tuberculosis vaccine: A review
Nur Ellene Mat LUWI ; Suhana AHMAD ; Ahmad Suhaimi Nurfatihah AZLYNA ; Asyikin NORDIN ; Rohimah MOHAMUD ; Ramlah KADIR ; Maria Elena SARMIENTO ; Armando ACOSTA ; Mohd Nor AZMI ; Vuk USKOKOVIĆ ; Vuk USKOKOVIĆ
Asian Pacific Journal of Tropical Medicine 2022;15(1):7-16
Liposomes are phospholipid bilayer vesicles, which are biocompatible, biodegradable and nontoxic vehicles suitable for numerous drug and gene delivery applications. In this review, we discuss the prospect of using liposome technology in the development of a vaccine for tuberculosis. Tuberculosis remains an important health problem that requires the development of an effective vaccine, especially since the only approved vaccine for it continues to be the Bacille Calmette-Geurin (BCG) one developed 100 years ago. This review focuses on the different applications of liposomes toward achieving this goal. Numerous liposomal formulations showing prospect in the research stage and in clinical trials are discussed.
6. Recognition of a multiple antigen peptide containing sequence from mimotope of the dengue type 3 virus NS4B protein by human antibodies
Nevis AMIN ; Alicia AGUILAR ; Rolando OCHOA ; Armando ACOSTA ; Maritza PUPO ; Susana VÁZQUEZ ; Yamira CABALLERO ; María G. GUZMÁN
Asian Pacific Journal of Tropical Medicine 2016;9(2):130-133
Objective: To evaluate the recognition of NS4B mimotope, as multiple antigen peptide (MAP), by dengue antibodies presents in serum samples from patients with different serotype infections. Methods: A MAP containing mimotope sequence was synthesized and used to evaluate the recognition of NS4B mimotope as MAP by a panel of 66 human sera from dengue cases by an indirect ELISA assay. Results: The MAP differentiated between sera from dengue viruses infected patients and sera from healthy individuals and the best reactivity was shown by serum from dengue type 3 virus patients. The recognition was more intense with serum from patients with secondary infection. Conclusions: The findings suggest the potential use of NS4B mimotope on the development of a multi-epitope diagnostic tool. These results are important for further immunogenicity studies.