, , , , ,

Most vaccines only target the B cells‘. No, there’s a great variety among vaccines. Whole inactivated or live attenuated vaccines target various arms of the immune system. Thus, such vaccines efficiently stimulate B, CD4 helper T and CD8 cytotoxic killer T cells. Examples include BCG for tuberculosis, a bacterium, and the vaccine for Yellow Fever, a virus.

Even vaccines that target B cells can only do so by targeting CD4 helper T cells as well, which, as their name suggests, help. When a naive B cell binds to an antigen it’s specific for, it’ll secrete IgM. Having low affinity for antigen, IgM has limited effectiveness. To more effectively target and eliminate an antigen, a B cell needs to undergo class-switch recombination (CSR, Immunoglobulin class switching) and Affinity maturation. CSR endows the B cell to switch from IgM to IgG, IgA or IgE while affinity maturation increases antibody affinity, i.e., the strength of antibody binding to antigen. Both processes facilitate more efficient antigen clearance by antibody, and both processes require CD4 helper T cells helping B cells. Thus, a vaccine that drives robust B cell responses, especially class-switched, high affinity antibody responses, needs to have strongly stimulated CD4 T cells as well. Conversely a vaccine that’s poor at inducing class-switched, high affinity B cell antibody responses would ipso facto be poor at stimulating CD4  helper T cells as well.

Problem arises with newer, sub-unit vaccines. Developed in response to regulatory pressures to create better defined vaccines, they’re conundrums because though inducing fewer vaccine site responses they’re also less immunogenic. With a regulatory and cultural landscape far different from the early vaccine era and much less likely to approve vaccines consisting of whole inactivated or live attenuated microbes, we are thus stuck between a rock and a hard place. The reductionist process involved in creating better defined vaccines tended to create duds, i.e., vaccines that didn’t work as well as their earlier, cruder counterparts. Thus started the process of adjuvanting such reductionist vaccines. Adjuvant, Immunologic adjuvant or the immunologist’s ‘dirty little secret‘ as Charles Janeway described them, trigger the innate immune system, which in turn is necessary to effectively engage the adaptive (CD4, CD8, B cells).

Problem is until recently the only adjuvants approved for use in humans, namely, Alum, i.e., aluminium salts, stimulate B cells and promote B cell-helping CD4 helper T cell responses. OTOH, alum-adjuvanted vaccines are poor at stimulating CD8 cytotoxic killer T cell responses, either directly or indirectly. So issue with most adjuvanted sub-unit vaccines is imbalance consisting of their robust capacity to drive B cell responses versus a relatively poor capacity to stimulate CD8 responses. This is a major gap in vaccines because CD8s are key for controlling and even eliminating many viruses. This in turn drives research to develop adjuvants with the capacity to support robust stimulation of CD8s. Among such newer adjuvants, ISCOM were endowed with the most potent capacity to trigger CD8s. However, their manufacture couldn’t be optimized for reproducibility and scale so they fell out of favor and the hunt for an optimal CD8 adjuvant continues.

See this answer for the history of how alum got added to vaccines: Tirumalai Kamala’s answer to Why is there aluminum in vaccines?

See this answer for how better defined vaccines yield the collateral cost of less efficacy and thus, poorer protection against their infectious disease targets as exemplified by pertussis vaccines: Tirumalai Kamala’s answer to Why is the pertussis vaccine not protecting those vaccinated for pertussis?