Question

What PAMPs or PAMP subunits do you think would be good adjuvants to enhance the immune response to vaccines in general and that might enhance the immune response to future Mycobacterium tuberculosis and HIV vaccines? 400 words

Answer 1

Pathogen associated molecular patterns(PAMPs) and PAMPs subunits of adjuvants have been traditionally used to increase the magnitude of an adaptive response to a vaccine through antibody titer or ability to prevent infection.

Some of the PAMPs or PAMPs subunits used commonly in clinics are Monophosphoryl lipid A and CpG-ODN and a combination of hydroxypropyl-β-cyclodextrin (HP-β-CyD) with a humanised TLR9 agonist, K3CpG-ODN has been proved as good adjuvants to enhance the immune response to vaccines.

Some of the roles of adjuvants in enhancing the immune response to vaccines in general are

(1)increase the response to a vaccine in the general population, increasing mean antibody titers and/or the fraction of subjects that become protectively immunized;

(2) increase seroconversion rates in populations with reduced responsiveness because of age, disease, or therapeutic interventions, as in the use on the MF59 adjuvant to enhance the response of older subjects to influenza vaccine.

(3) facilitate the use of smaller doses of antigen because the ability of an adjuvant to permit comparable responses with substantially lower amounts of antigen could be important in circumstances in which large-scale vaccination is urgent and production facilities limiting, as in the emergence of a pandemic influenza strain;

(4) permit immunization with fewer doses of vaccine. The requirement of many vaccines for multiple injections presents compliance issues and, in much of the world, significant logistic challenges. Adjuvants can reduce the number of doses required to achieve protection.

Some researchers have proposed the widespread use of adjuvants such as liposomes prepared of the quaternary ammonium compound dimethyl dioctadecyl ammonium (DDA). DDA induced a Cell mediated response (CMI)-response with secretion of Interferon Gamma IFN-γ and combining DDA with mixture of mycobacterial proteins, provided significant protection against Mycobacterium tuberculosis.

Adjuvants can be used to create broad and neutralizing immunity to HIV by invoking innate signaling mechanisms . For humoral responses, B cells must expand and undergo affinity maturation in order to recognize a diverse set of antigens. TLR4 adjuvant may be a key regulator in creating high affinity B cells as it has been demonstrated that these agonists alter B cell trafficking and result in a broadly neutralizing immune response.