Hypothesis driven development of new adjuvants

Abstract

To date, vaccinations have been one of the key strategies in the prevention and protection against infectious pathogens. Traditional vaccines have well-known limitations such as safety and efficacy issues, which consequently deems it inappropriate for particular populations and may not be an effective strategy against all pathogens. This evidence highlights the need to develop more efficacious vaccination regiments. Higher levels of protection can be achieved by the addition of immunostimulating adjuvants. Many adjuvants elicit strong, undefined inflammation, which produces increased immunogenicity but may also lead to undesirable effects. Hypothesis driven development of adjuvants is needed to achieve a more specific and directed immune response required for optimal and safe vaccine-induced immune protection. An example of such hypothesis driven development includes the use of short immunomodulating peptides as adjuvants. These peptides have the ability to influence the immune response and can be extrapolated for adjuvant use, but requires further investigation.

Literature review in support of adjuvanticity/immunogenicity assessment of proteins

“…While different studies are valuable to understand how immunity is controlled, it is still apparent and a major problem in the field of immunology which of the many processes dominates in different circumstances and even what is the final effect of the body in terms of increase or decrease of the immune response 85,94,125,163,178,[252][253][254][255][256][257][258][259][260][261][262][263][264] . While different studies are valuable to understand how immunity is controlled, it is still apparent and a major problem in the field of immunology which of the many processes dominates in different circumstances and even what is the final effect of the body in terms of increase or decrease of the immune response 85,94,125,163,178,[252][253][254][255][256][257][258][259][260][261][262][263][264] .…”

“…The injection of immunoglobulin (Ig) molecules intravenously has been found to reduce inflammation in autoimmune patients and in mouse models of autoimmunity Decrease response 271,272 Protein allergens EFSA "Scientific Opinion on the evaluation of allergenic foods and food ingredients for labelling Increase response/Allergens 255,273 www.efsa.europa.eu/publications 32 EFSA Supporting publication 2019:EN-1551…”

“…Many adjuvants elicit strong, undefined inflammation, which produces increased immunogenicity but may also lead to undesirable effects Increase response/Adjuvant 255 Many adjuvants elicit strong, undefined inflammation, which produces increased immunogenicity but may also lead to undesirable effects Increase response/Adjuvant 255 …”

Advances in the study of HLA-restricted epitope vaccines

“…69 Muderspach et al conducted a Phase I trial to evaluate the peptide vaccines HPV16 E7 [12][13][14][15][16][17][18][19][20] and E7 [86][87][88][89][90][91][92][93] . 70 These researchers immunized 18 HLA-A2-positive women with high-grade cervical or vulvar intraepithelial neoplasia who were positive for HPV16.…”

“…These observations have led to investigations on co-administration of adjuvants with vaccine antigens to potentiate the weak immunogenicity of the synthetic epitopes. 91 Adjuvanting antigens contribute to the success of vaccination. For example, 3-deacylated monophosphoryl lipid A (MPL), which is a detoxified derivative of the lipopolysaccharide from Salmonella minnesota R595, is a Toll-like receptor (TLR)-4 agonist and thus a potent activator of Th1 responses.…”