Development Of Innovative Vaccines Research Articles

Editorial Commentary: The Endgame for Serogroup A Meningococcal Disease in Africa?

Editorial Commentary: The Endgame for Serogroup A Meningococcal Disease in Africa?

Study of cynomolgus monkey (Macaca fascicularis) Mhc DRB gene polymorphism in four populations

The cynomolgus macaque (Macaca fascicularis) is currently used as an animal model in various fields of immunology especially in the development of innovative vaccines for the prevention and treatment of infectious diseases. The polymorphism of the major histocompatibility complex (MHC) influences the development of adaptive immune responses, and it is crucial to characterize the polymorphism of cynomolgus MHC genes. Among all macaque species, the cynomolgus macaque has the most diversified geographical area encompassing continental and insular populations. By the study of a large sample of animals from the Philippines (N = 359), we have characterized 20 DRB haplotypes. The DRB genotyping was performed by denaturing gradient gel electrophoresis (DGGE) sequencing of exon 2 and was confirmed by polymerase chain reaction-sequence-specific oligonucleotide. The DRB and DRA cDNA of 126 animals were characterized by cloning and sequencing. By means of DGGE sequencing, we characterized the polymorphism of genomic DRB exon 2 in three other cynomolgus macaque population samples (Java, Vietnam, and Mauritius), and we discuss about the origin of the founders of the Mauritian and the Filipino cynomolgus macaque populations.

PLGA, PLGA-TMC and TMC-TPP Nanoparticles Differentially Modulate the Outcome of Nasal Vaccination by Inducing Tolerance or Enhancing Humoral Immunity

Development of vaccines in autoimmune diseases has received wide attention over the last decade. However, many vaccines showed limited clinical efficacy. To enhance vaccine efficacy in infectious diseases, biocompatible and biodegradable polymeric nanoparticles have gained interest as antigen delivery systems. We investigated in mice whether antigen-encapsulated PLGA (poly-lactic-co-glycolic acid), PLGA-TMC (N-trimethyl chitosan) or TMC-TPP (tri-polyphosphate) nanoparticles can also be used to modulate the immunological outcome after nasal vaccination. These three nanoparticles enhanced the antigen presentation by dendritic cells, as shown by increased in vitro and in vivo CD4+ T-cell proliferation. However, only nasal PLGA nanoparticles were found to induce an immunoregulatory response as shown by enhanced Foxp3 expression in the nasopharynx associated lymphoid tissue and cervical lymph nodes. Nasal administration of OVA-containing PLGA particle resulted in functional suppression of an OVA-specific Th-1 mediated delayed-type hypersensitivity reaction, while TMC-TPP nanoparticles induced humoral immunity, which coincided with the enhanced generation of OVA-specific B-cells in the cervical lymph nodes. Intranasal treatment with Hsp70-mB29a peptide-loaded PLGA nanoparticles suppressed proteoglycan-induced arthritis, leading to a significant reduction of disease. We have uncovered a role for PLGA nanoparticles to enhance CD4+ T-cell mediated immunomodulation after nasal application. The exploitation of this differential regulation of nanoparticles to modulate nasal immune responses can lead to innovative vaccine development for prophylactic or therapeutic vaccination in infectious or autoimmune diseases.

Utility of virosomal adjuvated influenza vaccines: a review of the literature.

In spite of the efforts of the World Health Organization (WHO), influenza continues to be a major public health problem, both because of its impact on the health of subjects at risk, such as the elderly, and because of the economic burden that it places on society. Adjuvants are agents which, when incorporated into vaccines, enhance the immunogenicity of their antigens. The need for ever more immunogenic and efficacious influenza vaccines has led to the development of innovative vaccines. One of these, the virosomal vaccine, has been on the market since 1997. The results obtained through controlled clinical studies and widespread application in the field suggest that the virosomal vaccine is not only an important tool for the prevention of seasonal influenza but also a valid means of potentiating the effect of a pandemic influenza vaccine and, perhaps, of preparing multivalent or combined vaccines.

Challenges and potential solutions to innovative vaccine development for developing countries

Introduction. One of the barriers to meeting Millennium Development Goal Number 4 is access for large populations of developing countries to vaccines against their most serious and common diseases. Innovative vaccines have been more readily available at affordable prices once more producers enter the market, but this means that there will be a delay in access until these manufacturers can access the technology. Several solutions to enhance access have been proposed; none so far is optimal.Methods. The factors relating to competition in the market and an affordable price were examined. Historical price data to countries were reviewed. Various explanations for lack of competition were also analyzed, including unequal access to financing, lack of optimal research and development capacity, barriers to technology transfer, issues in accessibility to intellectual property.Results. Differences in vaccine scale up, know-how, GMP practices and regulatory oversight are decreasing between emerging suppliers and established multinationals. Developing country vaccine prices are at about the same levels for all manufacturers, but the level of vaccine development is lower for emerging suppliers who have few high priced markets to offset investments. There appear to be three major differences between multinational manufacturers and emerging suppliers:(1) limited access to research results that lead to new vaccine constructs;(2) barriers to vaccine technology development relating to blocking intellectual property;(3) inability to spread the investments that would be incurred in addressing issues (1) and (2) over a large enough financial base.In terms of pricing, experience with early adopting countries has shown that other factors may overcome the perceived pricing barrier: that is, willingness to pay appears not to correlate with country wealth.Conclusions. Based on these analyses it appears that the interventions of the international community might be better directed to achieve vaccine access.

Respiratory syncytial virus bronchiolitis: prevention and treatment

Background: Acute respiratory illness due to respiratory syncytial virus is one of the most common causes of hospitalization in very young children worldwide. The virus was discovered half a century ago, yet the underlying mechanisms of the disease are not fully understood and treatment remains supportive. Methods: This review article discusses therapeutic and preventive strategies, past, present and future, in the battle against respiratory syncytial virus. Conclusion: Prevention of severe respiratory syncytial virus infection in high-risk children can be achieved by the administration of specific monoclonal antibodies. Current issues include the management of respiratory syncytial virus infection in those with underlying immunological disease, the prevention of long-term airway morbidity and the development of innovative vaccines.

Managing the effect of TRIPs on availability of priority vaccines

The stated purpose of intellectual property protection is to stimulate innovation. The Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) requires all Members of the World Trade Organization (WTO) to enact national laws conferring minimum standards of intellectual property protection by certain deadlines. Critics of the Agreement fear that such action is inconsistent with ensuring access to medicines in the developing world. A WHO convened meeting on intellectual property rights and vaccines in developing countries, on which this paper is based, found no evidence that TRIPS has stimulated innovation in developing market vaccine development (where markets are weak) or that protection of intellectual property rights has had a negative effect on access to vaccines. However, access to future vaccines in the developing world could be threatened by compliance with TRIPS. The management of such threats requires adherence of all countries to the Doha Declaration on TRIPS, and the protections guaranteed by the Agreement itself, vigilance on TRIPS-plus elements of free trade agreements, developing frameworks for licensing and technology transfer, and promoting innovative vaccine development in developing countries. The role of international organizations in defining best practices, dissemination of information, and monitoring TRIPS impact will be crucial to ensuring optimal access to priority new vaccines for the developing world.

New vaccines against bacterial toxins.

Chemically detoxified bacterial toxins are the main or the sole components of several vaccines such as diphtheria, tetanus, pertussis, and cholera. Other toxins are good candidates for novel vaccines, such as the vacuolating cytotoxin of Helicobacter pylori 1. Recently, genetic manipulation of the toxin’s genes has been used to obtain molecules that are already non toxic and do not require chemical treatment for detoxification. This approach has been successful for pertussis2, diphtheria3, cholera and LT toxins4. Preclinical and clinical studies have shown that these molecules have several advantages over the conventional chemically detoxified vaccines. Generally, they are much more immunogenic and induce an immune response, that recognizes better the native toxin molecules. Non toxic derivatives of cholera toxin and LT, in addition to being good candidates for antidiarrheal vaccines, are also mucosal adjuvants5. Therefore, genetically detoxified bacterial toxins not only are good candidates to improve existing vaccines, but they represent new tools for the development of innovative vaccines targeted to the mucosal system.