vaccines have been developed for many infectious diseases since the early twentieth century and they have provided numerous benefits to human society . one of these benefits is the increased lifespan caused by the prevention of infectious diseases . however , the types of diseases have changed alongside the increased lifespan caused by the prevention of infectious disease . these new health threats are chronic diseases such as cancer , cardiovascular diseases , diabetes , and obesity . many therapeutic vaccine approaches have been developed for preventing chronic diseases . in this review , we discuss the prophylaxes and therapeutic vaccinations that could be used to reduce the incidence of obesity and diabetes . obesity is classified as one of the eight significant causes of chronic disease by the world health organization ( who ) . sixty - five percent of the world 's population lives in countries where overweight and obesity kills more people than underweight . the number of health problems linked to chronic diseases is increasing dramatically and obesity is related to numerous chronic diseases . many studies have also shown that obesity has a specific relationship with type 2 diabetes [ 4 - 6 ] . obesity causes many problems in humans , but the treatment options for obesity are very limited . it is widely accepted that a combination of dieting and physical activity is the most effective way of reducing obesity . thus , healthy practices are readily stopped and subjects may return to their previous weight , which is called the yo - yo effect . therefore however , current medications only have a beneficial effect if the treatment is sustained continuously . in addition , bariatric surgery may lead to permanent weight loss but this method has significant perioperative risks and an economic burden for the patient . to address the problems of obesity treatment , recent studies have shown that therapeutic vaccines may be new targets for the development of anti - obesity medications . the therapeutic vaccines could treat alternatively the obesity by suppressing the appetite - stimulating hormone and blocking absorption of nutrients . one therapeutic strategy is to block endogenous signals to reduce the appetite and body weight . in particular , immunization against the gut peptide , ghrelin , ghrelin is produced mainly in the small and large intestines , although it is also secreted by the lungs , pancreatic islets , gonads , kidney , and brain . in particular , it promotes weight gain by increasing the appetite and food intake , while reducing the energy expenditure . however this vaccine could cause emotional side effects . to identify the possibility of its use as a vaccine , synthetic ghrelin analogs were conjugated to haptens . mice immunized with the ghrelin peptide sequence gained less body weight and had lower body fat and circulating leptin levels . in addition , a therapeutic vaccine has been tested that used a noninfectious virus to carry ghrelin to elicit an immune response to obstruct this hormone . vaccinated mice had higher levels of anti - ghrelin antibodies compared with unvaccinated mice . moreover , the vaccinated mice had a lower food intake and increased energy expenditure , i.e. , obese mice had 82% of the food intake consumed by the control mice after the first vaccination injection and only 50% of the food intake of the control mice after the final vaccination . in addition , the vaccinated obese mice exhibited reduced neuropeptide y ( npy ) expression . npy is the most potent signal that increases the appetite via the central nervous system . furthermore , a ' flab jab ' vaccine has been reported that reduced the body weight by 10% four days after a single injection . the vaccine was designed to block the effects of somatostatin , which has many different functions in various organs . the release of somatostatin from the pancreas prevents insulin secretion and reduces the release of glucagon . blocking this growth hormone for example , vaccinated mice produced antibodies against somatostatin and their food intake was reduced compared with control mice at six weeks after vaccination . the vaccinated mice lost 12 - 13% of their body weight at four days after the first injection , although all of the mice consumed similar amounts of food . mice treated with the two vaccines , jh17 and jh18 , exhibited 4% and 7% increases in their body weight , respectively , compared with their body weight at the start of the study . by contrast , control mice exhibited a 15% increase in their body weight . however , this study had several limitations , such as problems with the control vaccination , the overall weight gain , and the unrealistic volume of vaccine required . in addition , this vaccine could cause steatorrhea , diarrhea , gastrointestinal cramps , and occasional nausea . therefore , somatostatin vaccines can reduce weight gain and the final body weight compared with the baseline weight , although there are some problems with this approach . the recombinant virus - like particle ( vlp ) has a similar structure to viruses but lacks sufficient genetic information to replicate . moreover , vlps derived from the coat protein of bacteriophage q have no preexisting immunity . during vlp assembly , single - stranded rna triggers toll - like receptors 7 and 8 , and these receptors induce co - stimulatory molecules and cytokines that promote antigen - specific igg2a responses . chemical conjugation can be used to attach antigens to the surface of q-vlp , thereby triggering potent antibody responses in animals and humans . in particular , vlp - based vaccines can induce antibodies against interleukin ( il)-1 to treat type 2 diabetes . the cytokine il-1 triggers islet cell apoptosis and is a primary agonist in the loss of beta cell mass in type 2 diabetes . therefore , the prevention of il-1 may improve the symptoms of type 2 diabetes patients . when mice were immunized with the full - length il-1 protein coupled to q-vlp , they produced high neutralizing antibody titers with specificity for il-1 . the antibody response against the mutant form of il-1 conferred protection in a rheumatoid arthritis animal model and the response also ameliorated the diabetic phenotype in a diet - induced obesity model . interestingly , the immune system is functionally linked to obesity . in particular , lymphoid tissues appear to be very sensitive to nutrient imbalances . therefore , these tissues have effects on metabolic pathways and the functions required for immune defense . in addition , it is well known that the effect to vaccination is reduced by obesity ( fig . 1 ) . a previous study demonstrated an association between low antibody levels , obesity , and the response to hepatitis b vaccines . another study showed that a standard hepatitis b vaccine had a 71% protection rate in obese adults ( body mass index > 30 ) compared with 91% in the healthy control group . a further study investigated the mechanism related to the reduced antibody response to vaccination , where ob / ob obese mice exhibited 21% and 12% lower levels of pre - b and immature b cells , respectively , compared with wild type c57bl/6 mice . these results indicate that obesity can modify the immune system to produce an immunodeficient state , including altered lymphocyte and monocyte functions . diet - induced and genetic obesity increase the susceptibility to bacterial and viral infections in humans and animals . therefore , it is necessary to perform intensive studies to determine the effects of obesity on the efficacy of vaccinations . recently , many studies have reported that infections with pathogens can induce obesity and metabolic diseases . thus , preventing and treating infection by selected pathogens may help to reduce the risk of the adverse effects of obesity . of the known obesity - inducing pathogens , human ad36 induces adiposity but paradoxically it improves insulin sensitivity [ 36 - 38 ] . ad36-infected animals have a higher body weight and fat content , but hypolipidemia compared with control animals . there is a strong association between ad36 infection and human obesity [ 36 - 38 ] . ad36 is a human adenovirus that belongs to serotype d and it is antigenically distinct . according to epidemiological data , 30% of obese and 11% of non - obese adults in the united states possess antibodies against ad36 . moreover , it has been reported that there is a relationship between viral infections with ad36 and obesity in several nations [ 41 - 44 ] . however , research into the treatment of viral infections and vaccine development is still lacking in this area . a previous study tested the possibility of using an inactivated ad36 vaccine , where ad36 was inactivated using ultraviolet ( uv ) irradiation . in trials , mice were inoculated with live ad36 , uv - inactivated ad36 , or the medium alone . live ad36 increased the size of the epididymal fat pad at 4 days post - inoculation , whereas uv - inactivated ad36 did not cause an increase . furthermore , our group demonstrated a ' proof of concept ' using an ad36 vaccine ( unpublished data ) . we injected mice with uv - inactivated ad36 , live ad36 as the positive control , and medium as the negative control , before challenge with live ad36 ( unpublished data ) . the mice were sacrificed and their organs were used to study the chronic effects at 90 days post - challenge . live ad36-injected mice had larger epididymal fat pads and exhibited inflammation of their fat deposits . however , the body weight and epididymal fat levels of the uv - inactivated ad36-injected mice were similar to those of the control mice . moreover , treatment with uv - inactivated ad36 decreased the level of inflammation in the fat deposits . overall , these results show that uv - inactivated ad36 can prevent increases in body fat and inflammation hormones have been tested as targets to treat ' conventional ' obesity by developing therapeutic vaccines . the incidence of pathogen - induced obesity is increasing , but the development of vaccines to treat these pathogens is insufficient at present . several studies have demonstrated the ' proof of concept ' of the potential application of a prophylactic vaccine against ad36 as an anti - obesity agent . an inactivated ad36 vaccine can prevent increases in the body weight and fat content , as well as reducing inflammation in fat deposits . however , this type of anti - obesity vaccine research is just beginning . therefore , more intensive studies are required to develop prophylactic and therapeutic vaccines to prevent obesity .