Hepatitis B needle-free vaccines: a step closer (2011)

Since the time of Edward Jenner and his discovery of the smallpox vaccine, and during the 200 years that have followed, vaccination has been successfully applied to protect against some of the most important infectious diseases. Moreover, in the case of smallpox, the dream of eradication of a pathogen causing a potentially deadly disease, especially in infants, has come true, with the last case of natural contraction of smallpox observed in 1977 in Somalia [101]. The only other eradicated disease is rinderpest, as will be officially announced by the UN in 2011 [1]. In campaigns to eradicate smallpox, the vaccine was administered using a bi furcated needle or a needle-free jet injector. Both devices deposit the antigen in the subcutaneous tissue. Curiously, before Jenner, a Chinese medical text described several ways of inoculation against smallpox practiced in China. In one of the methods, the nose was plugged with powdered scabs on cotton wool [102]. In another, white cow fleas were ground into powder and made into pills. These may have been the first attempts to formulate a vaccine to be applied by mucosal routes (intranasal and oral, respectively). We may therefore consider that needle-free vaccines were developed even before injectable vaccine formulations, possibly caused by the lack of technology available. At present, the term ‘vaccination’ is generally considered to be equal to ‘injection’. This conception is due to the fact that vaccines are typically given by intramuscular injection. By analyzing some of the exceptions in the market, such as the polio and rotavirus oral vaccines, it can be observed that both contain the live attenuated virus, which does explain, at least in part, the strong immune response observed after oral administration of these vaccines. In the new era of vaccine development, with the emergence of subunit vaccines, the formulation of needle-free vaccines is undoubtedly more challenging. Novel vaccines obtained by recombinant technology are, in principle, safer with regards to toxicity; however, they are also less immunogenic, making it mandatory to include adjuvants in the formulation of such vaccines. The hepatitis B vaccine, licensed in 1981, was the world’s first recombinantly expressed plasma-derived subunit vaccine. Despite being on the market for over 30 years, the European Centre for Disease Prevention and Control estimates a prevalence of 8000 newly diagnosed cases of hepatitis B in the EU alone [103]. Numerous efforts made by the scientific community to develop needle-free vaccine formulations are justifiable by several distinct advantages. An obvious one is the possibility of painless self administration of the vaccine. Moreover, vaccine delivery via mucosal surfaces elicits mucosal immune responses at the site of pathogen entry as well as enhanced cellular immunity through Toll-like receptors stimulation [2], thus improving overall effectiveness. Since the hepatitis B virus can be transmitted perinatally or by exchange of body fluids (e.g., blood, semen and vaginal fluid), the design of new hepatitis B vaccines with the additional possibility to induce mucosal