A vaccine can be an effective strategy to control arbovirus infections. Although vaccines are available for yellow fever and Japanese Encephalitis Viruses there is no specific vaccine available for the treatment of other arboviruses except. Yellow fever vaccine is a live attenuated virus from the 17D lineage, a single dose of this vaccine can provide protection from infection up to 10 years. However, to maintain a lifelong protection from yellow fever infection in the endemic area a booster dose after every 10 years is required60 .
The development of a yellow fever vaccine has protected millions of human population from potentially fatal infection. In case of JE Virus, four different type of vaccines are available, mouse brain-derived killed vaccine, cell culture-derived killed vaccine, cell culture-derived attenuated vaccine, and genetically engineered live attenuated chimeric vaccine 61. The first vaccine developed against JEV is mouse brain-derived vaccine was first used in Japan in 1954 62 later this vaccine was replaced by cell culture-based live attenuated and killed vaccine. Genetically engineered live attenuated chimeric vaccine (IMOJEV, JE-CV and THAIJEV), are commercially available in Australia and Thailand 62,63. A single dose of this vaccine has provided nearly complete (99%) seroconversion in adults.
In Phase II trial this vaccine provided protection against JEV infection for approximately 5 years in 87% of the vaccine recipients64. In last decades, great efforts have been made to develop a vaccine against dengue virus. Although there are few vaccine candidates are in various stages of development 65. Still, there are not a single commercially available vaccines against dengue virus.
It has been reported that primary infection with one type of dengue serotype can provide lifelong protection against that particular serotype (homotypic immunity) 66 and cross-protection for other serotypes for around 2 years 67. However, after that period the person is still susceptible to dengue infection by other serotype and in some cases, it increases the severity of subsequent infection 68. This homotypic protection against dengue virus serotype is one of the important factors to be considered while developing an effective vaccine against dengue virus. The first dengue vaccine, which is licensed for phase 3 clinical trials, is Dengavaxia® (CYD-TDV) developed by Sanofi Pasteur 69,70. It is a tetravalent, live attenuated containing four recombinant yellow fever 17D strain expressing prM and E protein from each dengue serotype. Dengvaxia® has been evaluated in two phase 3 clinical trials known as CYD 14 and CYD 15.
CYD 14 trial was conducted in 5 dengue endemic Asian countries (Indonesia, Malaysia, Philippines, Thailand and Vietnam) 71, whereas, CYD 15 trial was conducted in 5 dengue endemic Latin American countries i.e. Brazil, Colombia, Honduras, Mexico and Puerto Rico 72. The protective efficacy of Dengavaxia® for dengue infection was estimated to range from 50.2% to 76.6 % for individuals from different age group and serotypes 73. In silico modelling has suggested that the introduction of Dengvaxia® vaccine at early adolescence stage could result in the reduction in dengue hospitalizations by 10-30% over time 70.
In addition to Dengvaxia®, other potential dengue vaccine candidates are in the process of development or are in clinical trials 65,70.One potential vaccine candidate developed by National Institute of Health, USA, is a live attenuated (recombinant) vaccine. TV003 and TV005 which are identical vaccine candidates except for the dose level of the DEN2 component were based on wild-type strains mutated to attenuate the virus 28. Another potential vaccine candidate DENVax, is a tetravalent vaccine using DENV-2 and recombinant prM and E proteins of rest three serotypes. Both vaccine candidate has shown promising results and now are in phase 2 trials 74-76. Similar to dengue virus, there is no vaccine available against CHIKV infection. However, prospects look good because there are more than 15 vaccine candidates against CHIKV infection are in various stages of development. These vaccine candidates are based on various platforms such as, inactivated, live attenuated, chimeric, subunit protein and DNA based vaccine 77.
Although research is yielding important insights, most of the candidate’s vaccine are in preclinical stages and only a few have reached to phase 1 clinical trials 77.Availability of an effective vaccine can become a powerful tool to fight mosquito-borne viral diseases, however, a details risk assessment in geographically diverse population has to be performed prior to approval for public use.The conventional vaccine can only protect individuals from infection, but mosquito carrying arbovirus can transmit the virus to unvaccinated individuals. A vaccine which can prevent or block transmission cycle of pathogen inside mosquito vector is an alternate approach to stop arbovirus transmission in humans78. Research has been conducted to develop broad-spectrum Transmission Blocking Vaccine (TBV) 51. The difference between conventional and TBV is their mode of action, TBV prevents infection in mosquito vector in place of its human or animal hosts and blocks the further transmission in the mosquito.
60. A potential protein candidate for a TBV against DENV infection is the putative cysteine-rich venom protein 379 (CRVP379) is important for DENV infection; silencing CRVP379 resulted in reduced DENV infection in Ae. aegypti mosquitoes.
Antibodies against CRVP379 could bound the native CRVP379 protein in mosquito gut, which eventually resulted in transmission disruption of dengue virus 50. Another TBV molecule identified is protein Pfs25 is able to prevent the acquisition of malaria from infected mice by female mosquitoes 79. Similarly, mice vaccinated with Serpin-2 protein has prevented Plasmodium berghei acquisition in Anopheles mosquitoes 80. TBVs has the potential to decrease arbovirus load in the wild mosquito population, which will also increase herd immunity and can be an effective tool to fight arbovirus infection. Available data has suggested that a single TBV vaccine may develop, which can provide protection from multiple viral agents.