10-02-2013, 09:07 PM
New research on vaccine adjuvants
The original article in this thread outlines the importance of adjuvants in enhancing vaccine effectiveness. In maximising the immunogenicity of vaccines, an effective adjuvant can allow the dose or number of administrations of the vaccine to be reduced, thus making the whole process more cost-effective and helping overcome issues associated with limited worldwide availability of various vaccines.
As mentioned, aluminium-containing adjuvants are the most commonly used in human vaccines. Despite this, the mechanisms of action of these adjuvants are not well understood. A study from Purdue University in the USA looked at kinetics of the inflammatory response in mice after intramuscular injection of an aluminium adjuvant. They found that in naïve mice, inflammatory cells accumulated at the injection site within 2-6 hours, at first dominated by neutrophils, with later accumulation of macrophages, eosinophils and antigen-presenting cells. In previously immunised mice, the accumulation of macrophages, eosinophils and antigen-presenting cells was more rapid and robust and coincided with accumulation of chemokines.
Research is on-going to identify other effective, novel adjuvants. In a study on rhesus macaques from Merck Research Laboratories in Pennsylvania in the USA, a saponin-based adjuvant called ISCOMATRIXTM was found to be more effective than either aluminium hydroxylphosphate sulphate or a synthetic TLR9 agonist as an adjuvant for a novel rabies vaccine. This is relevant in the context of worldwide supply issues of rabies vaccine.
Another study from Universidad Nacional Autónoma de México examined a novel synthetic peptide GK-1, derived from Taenia crassiceps fused to the pVIII protein of a heat-inactivated phagemid vector (FGK1) as an adjuvant when co-administered to mice or pigs with influenza vaccine. They found that in pigs, for example, one dose of FGK1 and influenza vaccine induced comparable serum levels of IgG anti-influenza to two doses of influenza vaccine alone. This peptide fusion is a potentially low-cost adjuvant and is currently in testing for veterinary purposes.
A third study from Shandong University in China evaluated dendritic cell vaccines for cervical cancer. Dendritic cells were loaded with human papillomavirus type 16 (HPV16) peptides and administered with a CpG oligodeoxynucleotide (CpG-ODN) as adjuvant. In vivo mice studies and in vitro studies gave encouraging results in terms of immunogenicity as assessed by IL-12 levels, the allogeneic T cell-stimulatory capacity and the cytotoxicity of cytotoxic T lymphocytes (CTLs) in vitro and tumour sizes, expression of IgG and IFN-γ, and the presence of human T cells in vivo.
Clearly development of adjuvants is a field with promise for exciting new prospects.
Sources
DISTEFANO, D. et al., 2013. Immunogenicity of a reduced-dose whole killed rabies vaccine is significantly enhanced by ISCOMATRIX adjuvant, Merck amorphous aluminum hydroxylphosphate sulfate (MAA) or a synthetic TLR9 agonist in rhesus macaques. Vaccine, 31(42), pp. 4888-4893
LU, F. and HOGENESCH, H., 2013. Kinetics of the inflammatory response following intramuscular injection of aluminum adjuvant. Vaccine, 31(37), pp. 3979-3986
SEGURA-VELÁZQUEZ, R. et al., 2013. Influenza vaccine: development of a novel intranasal and subcutaneous recombinant adjuvant. Vaccine, 31(37), pp. 4009-4016
WANG, H.L. et al., 2013. In vitro and in vivo evaluations of human papillomavirus type 16 (HPV16)-derived peptide-loaded dendritic cells (DCs) with a CpG oligodeoxynucleotide (CpG-ODN) adjuvant as tumor vaccines for immunotherapy of cervical cancer. Springer Verlag.
The original article in this thread outlines the importance of adjuvants in enhancing vaccine effectiveness. In maximising the immunogenicity of vaccines, an effective adjuvant can allow the dose or number of administrations of the vaccine to be reduced, thus making the whole process more cost-effective and helping overcome issues associated with limited worldwide availability of various vaccines.
As mentioned, aluminium-containing adjuvants are the most commonly used in human vaccines. Despite this, the mechanisms of action of these adjuvants are not well understood. A study from Purdue University in the USA looked at kinetics of the inflammatory response in mice after intramuscular injection of an aluminium adjuvant. They found that in naïve mice, inflammatory cells accumulated at the injection site within 2-6 hours, at first dominated by neutrophils, with later accumulation of macrophages, eosinophils and antigen-presenting cells. In previously immunised mice, the accumulation of macrophages, eosinophils and antigen-presenting cells was more rapid and robust and coincided with accumulation of chemokines.
Research is on-going to identify other effective, novel adjuvants. In a study on rhesus macaques from Merck Research Laboratories in Pennsylvania in the USA, a saponin-based adjuvant called ISCOMATRIXTM was found to be more effective than either aluminium hydroxylphosphate sulphate or a synthetic TLR9 agonist as an adjuvant for a novel rabies vaccine. This is relevant in the context of worldwide supply issues of rabies vaccine.
Another study from Universidad Nacional Autónoma de México examined a novel synthetic peptide GK-1, derived from Taenia crassiceps fused to the pVIII protein of a heat-inactivated phagemid vector (FGK1) as an adjuvant when co-administered to mice or pigs with influenza vaccine. They found that in pigs, for example, one dose of FGK1 and influenza vaccine induced comparable serum levels of IgG anti-influenza to two doses of influenza vaccine alone. This peptide fusion is a potentially low-cost adjuvant and is currently in testing for veterinary purposes.
A third study from Shandong University in China evaluated dendritic cell vaccines for cervical cancer. Dendritic cells were loaded with human papillomavirus type 16 (HPV16) peptides and administered with a CpG oligodeoxynucleotide (CpG-ODN) as adjuvant. In vivo mice studies and in vitro studies gave encouraging results in terms of immunogenicity as assessed by IL-12 levels, the allogeneic T cell-stimulatory capacity and the cytotoxicity of cytotoxic T lymphocytes (CTLs) in vitro and tumour sizes, expression of IgG and IFN-γ, and the presence of human T cells in vivo.
Clearly development of adjuvants is a field with promise for exciting new prospects.
Sources
DISTEFANO, D. et al., 2013. Immunogenicity of a reduced-dose whole killed rabies vaccine is significantly enhanced by ISCOMATRIX adjuvant, Merck amorphous aluminum hydroxylphosphate sulfate (MAA) or a synthetic TLR9 agonist in rhesus macaques. Vaccine, 31(42), pp. 4888-4893
LU, F. and HOGENESCH, H., 2013. Kinetics of the inflammatory response following intramuscular injection of aluminum adjuvant. Vaccine, 31(37), pp. 3979-3986
SEGURA-VELÁZQUEZ, R. et al., 2013. Influenza vaccine: development of a novel intranasal and subcutaneous recombinant adjuvant. Vaccine, 31(37), pp. 4009-4016
WANG, H.L. et al., 2013. In vitro and in vivo evaluations of human papillomavirus type 16 (HPV16)-derived peptide-loaded dendritic cells (DCs) with a CpG oligodeoxynucleotide (CpG-ODN) adjuvant as tumor vaccines for immunotherapy of cervical cancer. Springer Verlag.
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