September 18, 2017 – Effect of endotoxin and alum adjuvant vaccine on peanut allergy “OVA/alum vaccines were administered subcutaneously to provide alum exposure before gastric peanut sensitization to evaluate alum’s influence on allergen hypersensitivity. Although TH1-inducing adjuvants used prophylactically or coadministered with allergens reduce the development of allergen-specific hypersensitivity reactions in mice, widespread prophylaxis with TH1-inducing adjuvants to reduce the development of allergy in human subjects is not practical. However, it might be practical to modify current vaccine formulations to contain alum and TH1-biased adjuvants to induce a balanced TH1/TH2 response and reduce the development of allergic disease. Therefore we evaluated the TH1-inducing adjuvants MPL or CpG combined with alum for their ability to enhance OVA-specific TH1 responses and influence peanut allergy outcomes.”
August 23, 2016 – Nanovaccine could enhance cancer immunotherapy, reduce side effects “One approach to immunotherapy has been to introduce a foreign substance into the body called unmethylated cytosine-guanine oligodeoxynucleotides (or CpG). CpGs are distinct patterns of DNA sequences that occur in bacteria but are rare in mammals. When injected into humans, CpGs act as a danger signal that triggers an immune response. Recently, a number of clinical trials have experimented with injecting CpGs directly into a tumor as a way to activate nearby immune cells so that they attack it.” Comment CpG adjuvants may cause autoimmunity See here.
January 11, 2016 – Proinflammatory Stimulation of Toll-Like Receptor 9 with High Dose CpG ODN 1826 Impairs Endothelial Regeneration and Promotes Atherosclerosis in Mice “Systemic stimulation of TLR9 with high dose CpG ODN impaired reendothelialization upon acute vascular injury and increased atherosclerotic plaque development in ApoE-/- mice. Further studies are necessary to fully decipher the contradictory finding of TLR9 agonism in vascular biology.”
May 8, 2015 – CpG Oligonucleotides as Cancer Vaccine Adjuvants “There is concern that inclusion of CpG ODN may increase the risk of vaccine-induced autoimmunity. CpG ODN and immune complexes that contain nucleic acids interact with TLR9 to increase the production of type I IFNs. While IFNa and IFNb can induce/exacerbate autoimmune disease, whether CpG based adjuvants have such an effect remains controversial, having not been observed in clinical vaccine trials. We conclude that when a vaccine against cancer capable of overcoming tolerance to tumor Ags is required, the benefit of including a strong adjuvant (such as CpG ODN) outweighs the potential risk. Comment: Clinical trials before vaccine approval does not account for ppost-approval adverse events when more of the population will be vaccinated. Who makes the judgement call that this adjuvant outweighs the risks?
May 18, 2011 – Production of antibodies with peptide-CpG-DNA-liposome complex without carriers (full text)
April 2011 – CpG DNA as a vaccine adjuvant. “The adjuvant properties of CpG are observed when administered either systemically or mucosally, and persist in immunocompromised hosts.”
April 19, 2010 – Emulsified Nanoparticles Containing Inactivated Influenza Virus and CpG Oligodeoxynucleotides Critically Influences the Host Immune Responses in Mice (full text) “So far as the safety issue is concerned, a claim was made that adjuvanted vaccines foster either accepted or hypersensitive autoimmune diseases due to boost the immune system of the body too much [3]. Of note, clinical studies also found that vaccines containing CpG arise to severe autoimmune disease, Wegener’s granulomatosis, in which blood vessels become inflamed.”
November 2009 – Neonate Intestinal Immune Response to CpG Oligodeoxynucleotide Stimulation (full text) Comment: 'Why would anyone allow a vaccine with an adjuvant known to cause an autoimmune disease to be given to their newborn baby?
August 2007 – Maximizing CD8+ T cell responses elicited by peptide vaccines containing CpG oligodeoxynucleotides
May 2007 – CpG Motip-Based Adjuvant Enhances immunogenicity of a Recombinant LHRH Vaccine and Noninvasive Monitoring of Adrenal and Gonadal Function in the Jaguar (Panthera onca) (pdf) “In relatively rare cases, the immune system mistakenly identifies non-foreign components as foreign, which results in autoimmune conditions.”
March 2005 – CpG Oligodeoxynucleotides as a Future Vaccine for Allergic Diseases (pdf) “In light of the pathogenic roles of Th1 cells in various types of autoimmunity, the effects of CpG motifs on the activation of autoreactive Th1 cells and autoimmunity are also unpredictable and controversial.”
February 2004 – CpG Oligodeoxynucleotide and Montanide ISA 51 Adjuvant Combination Enhanced the Protective Efficacy of a Subunit Malaria Vaccine (full text) “Protective immunity required Freund’s adjuvant; immunization in other adjuvant formulations failed to induce protection.”
January 25, 2004 – Lymphoid follicle destruction and immunosuppression after repeated CpG oligodeoxynucleotide administration
September 22, 2003 – Blood plasmacytoid dendritic cell responses to CpG oligodeoxynucleotides are impaired in human newborns (full text) “We conclude that beside the reduced production of IFN-γ production by CD4+ T cells and the impaired synthesis of IL-12p70 by myeloid DCs, deficient responses of pDCs also contribute to the immaturity of cell-mediated immunity in human newborns. These findings might be relevant to the increased susceptibility to infections as well as to the use of CpG oligodeoxynucleotides as vaccine adjuvants in the neonatal period.”
November 15, 2002 – Preclinical development of an adjuvant-free peptide vaccine with activity against CMV pp65 in HLA transgenic mice (full text) “Adjuvants, especially those that are oil-based or contain mycobacterial components, are permissible in animals, yet in many cases they are too inflammatory for human use… Alternative means to enhance the effectiveness of vaccinations with subunit protein and peptide vaccines in mice and primates using CpG (ODN) have been reported.
November 2002 – CpG-containing oligodeoxynucleotides, in combination with conventional adjuvants, enhance the magnitude and change the bias of the immune responses to a herpesvirus glycoprotein. “In this study, we compared various mineral oil, metabolizable oil and non-oil adjuvants alone and in combination with CpG ODN for their ability to augment immune responses to a truncated secreted form of bovine herpesvirus (BHV) glycoprotein D (tgD).” Comment: As if oil adjuvants alone and CpG adjuvants alone are not inflammatory enough, they are resarching ways to make new adjuvants that combine both of them.
June 18, 2002 – Use of nucleic acids containing unmethylated CpG dinucleotide as an adjuvant (patent)
August 10, 2001 – The Role of DNA Methylation in Mammalian Epigenetics “Methylation is also used for long-term epigenetic silencing of X-linked and imprinted genes and can either increase or decrease the level of transcription, depending on whether the methylation inactivates a positive or negative regulatory element.”
January 2001 – Whole blood cultures to assess the immunostimulatory activities of CpG oligodeoxynucleotides.
September 1999 – CpG DNA as mucosal adjuvant. We have previously found synthetic oligodeoxynucleotides (ODN) containing immunostimulatory CpG motifs to be a potent adjuvant to protein administered by intramuscular injection or intranasal inhalation to BALB/c mice. Herein we have further evaluated the potential of CpG ODN as a mucosal adjuvant to purified hepatitis B surface antigen (HBsAg) when administered alone or with cholera toxin (CT). CpG ODN and CT both augmented systemic (humoral and cellular) and mucosal immune responses against HBsAg, and these could be further enhanced with higher doses of adjuvant or boosting. Results from this study indicate that stimulatory CpG are promising new adjuvants for mucosal vaccination strategies, whether used alone or in combination with other mucosal adjuvants. Comment: This research is looking at the combined effect of cholera toxin, hepatitis b antigen and CpG. Really?
January 1999 – CpG motifs as immune adjuvants.
February 1988 – The CpG dinucleotide and human genetic disease. “These findings are consistent with methylation-induced deamination of 5-methyl cytosine and suggest that methylation of DNA within coding regions may contribute significantly to the incidence of human genetic disease.”