Therapeutic vaccines for chronic diseases: successes and technical challenges

Abstract

Chronic, non-communicable diseases are the major cause of death and disability worldwide and have replaced infectious diseases as the major burden of society in large parts of the world. Despite the complexity of chronic diseases, relatively few predisposing risk factors have been identified by the World Health Organization. Those include smoking, alcohol abuse, obesity, high cholesterol and high blood pressure as the cause of many of these chronic conditions. Here, we discuss several examples of vaccines that target these risk factors with the aim of preventing the associated diseases and some of the challenges they face.

Figure 1.

VLPs and the chemical coupling approach. The figure depicts a structural representation of a Qβ VLP obtained from the crystal structure of the phage Qβ. It also illustrates the modular approach to vaccine production whereby the protein antigen and VLP are separately produced and then covalently linked using a heterobifunctional chemical cross-linker such as succinimidyl-6-[(β-maleimidopropionamido) hexanoate] (SMPH). The resultant conjugate vaccine displays the target antigen in an ordered and highly repetitive fashion. Shown too is an electron-micrograph of 25–30 nm diameter icosahedral Qβ VLPs.

Figure 2.

Vaccination to prevent nicotine addiction. (a) Nicotine absorbed into the blood stream after smoking readily crosses the blood–brain barrier (BBB). Nicotine-specific antibodies induced by immunization with NiCQb bind nicotine in the blood. Because the antibody-sequestered nicotine is too large to cross the BBB, the flux of nicotine to the brain is inhibited. (b) Results from a phase II clinical study in smokers. 159 smokers receiving NicQb were classified into high, medium and low responders to the vaccine based on their anti-nicotine IgG titres. Thirty of the 53 high responders were continuously abstinent (non-smokers) compared with 31% in the placebo group. This result was highly statistically significant (p = 0.004) [28].

Figure 3.

Vaccination to treat hypertension. Profiles of mean hourly ambulatory blood pressure measurements from 21 individuals immunized with 300 µg of the anti-hypertension vaccine AngQb compared with the corresponding placebo group (n = 12) at week 14 of the phase II study. The difference from placebo in the change from baseline in mean ambulatory blood pressure at week 14 was −9.0/–4.0 mmHg (p = 0.015 for systolic blood pressure, p = 0.064 for diastolic blood pressure). The blood pressure surge between 5.00 and 8.00 h was reduced compared with placebo after baseline correction (p = 0.012 and p = 0.036, respectively) with a change at 8.00 h of −25 mmHg in systolic blood pressure (p < 0.0001) and −13 mmHg in diastolic blood pressure (p = 0.0035).

Figure 4.

Vaccination to prevent type II diabetes. Immunogenicity and specificity of anti-IL-1β IgG antibodies induced by immunization with IL1bQb. Mice (n = 5) were immunized on days 0, 21 and 42 with 300 µg of IL1bQb in alum. Sera were collected on day 56 and analysed by ELISA to measure anti-IL1β response and test cross-reactivity with IL-1α and IL-1 receptor antagonist (IL-1Ra).