Introduction
Togaviridae, Flaviviridae, Bunyaviridae, Reoviridae, and Rhabdoviridae are some of the ribonucleic acid (RNA) viruses that are maintained in nature as zoonoses and are known as arboviruses (arthropod-borne viruses) [1]. Arboviruses are viruses spread by hematophagous arthropods like mosquitoes, phlebotomine sandflies, ticks, and other vectors. The majority of arboviruses are maintained in nature via sylvatic complex maintenance cycles, in which hematophagous arthropods bite vertebrate hosts to spread the virus [2]. Due to their occasional disease outbreaks and epidemics that affect both human and animal populations, they place a heavy strain on global public health, society, and the economy. In particular, mosquito-borne viruses such those that cause dengue (DEN), chikungunya (CHIK), yellow fever (YF), Japanese encephalitis (JE), West Nile (WN), and Rift Valley fever (RVF) are a significant source of this burden [3]. Currently, more than 500 arboviruses (viruses carried by arthropods) have been discovered, and roughly 150 of them are responsible for human infection [4]. Blood-sucking arthropods have greatly expanded into new areas due to climate change, urbanisation, rising commerce, and worldwide travel brought on by globalisation [5]. Arboviral strains may be associated despite a wide range of clinical manifestations. Arboviruses may trigger a variety of diseases, including encephalitis, haemorrhagic fevers, and congenital anomalies, in addition to minor, self-limiting febrile infections [6]. Arboviruses have a significant influence on public health globally. Millions of individuals are annually infected by all of these viruses, placing an enormous strain on medical facilities, the economy, and rates of morbidity [7]. A multifaceted strategy is used to fight arboviruses, including vector management, public health surveillance, and—most importantly—the development of efficient vaccines and antiviral medications [8]. Arboviral infections have been fought with vector control techniques including pesticide spraying and vaccine development. While vaccines were successfully developed for some arboviruses, like yellow fever and Japanese encephalitis, others, including dengue and Zika, have proven to be more difficult to generate. Understanding and reducing the effect that arboviruses have on human health depends on the research of arboviruses and the way they interact with hosts and vectors [9].
Classification of arboviruses
The classification of arboviruses is grouped with their respective families as given in the table 1.
Table 1: Classification of arboviruses
|
Virus
|
Genus
|
Family
|
Vector
|
Disease
|
References
|
|
Dengue virus
|
Flavivirus
|
Flaviviridae
|
Aedes mosquitoes
|
Dengue fever
|
[7]
|
|
Zika virus
|
Flavivirus
|
Flaviviridae
|
Aedes mosquitoes
|
Zika fever
|
[10]
|
|
Chikungunya virus
|
Alphavirus
|
Togaviridae
|
Aedes mosquitoes
|
Chikungunya fever
|
[11]
|
|
West Nile virus
|
Flavivirus
|
Flaviviridae
|
Culex mosquitoes
|
West Nile fever
|
[12]
|
|
Yellow fever virus
|
Flavivirus
|
Flaviviridae
|
Aedes, haemagogus mosquitoes
|
Yellow fever
|
[13]
|
|
Rift valley virus
|
Phlebovirus
|
Bunyaviridae
|
Various mosquitoes
|
Rift valley fever
|
[14]
|
|
La Crosse virus
|
orthobunyavirus
|
Bunyaviridae
|
Aedes mosquitoes
|
La Crosse encephalitis
|
[15]
|
Global impact of arboviruses infections on public health
Arboviruses are a serious hazard to public health in all parts of the world and have a wide range of effects:
Disease burden: Arboviruses cause thousands of infections each year & have a substantial burden of disease [16]. Examples include the Zika virus, which attracted global attention owing to its relation to congenital malformations [10], which affects an estimated 390 million individuals each year, and the dengue virus, which is thought to infect 390 million people annually [7]. Numerous hospitalisations and even fatalities are brought on by these illnesses [17].
Economic impact: Arbovirus outbreaks entail significant adverse effects on the economy. The expense of medical care, vector control initiatives, and lost productivity because of disease can have a considerable negative impact on economy or systems of healthcare [18]. For instance, the 2015 Zika outbreak in the Americas was expected to have cost the global economy billions of dollars [19].
Disruption of healthcare systems: Arbovirus epidemics can overburden healthcare systems, resulting in a lack of medical resources and a pressure on healthcare personnel [20]. Impact on tourism, travel, maternal and child health: Travel and tourism frequently break in areas where arbovirus epidemics are common because people are hesitant to go to places where there is active transmission [21]. Congenital Zika syndrome, which is characterised by birth abnormalities in children born to women infected during pregnancy, emphasises the long-term implications of arbovirus infections [22].
Psychological and social impact: Infected populations may experience psychological suffering as a result of a rabies outbreak [23]. Arbovirus-related stigmatisation of victims and impacted communities is also a problem [24].
Epidemiology of arboviruses
Arboviruses have a tremendous impact on the world, with up to 700,000 fatalities annually linked to illnesses caused by arboviruses. Dengue virus (DENV), one of the mosquito-borne arboviruses, has a significant negative influence on public health, with over 390 million cases annually recorded, primarily impacting Asia and Latin America. Each year, the Yellow Fever Virus (YFV), which mostly affects Africa & Latin America, leads to approximately 200,000 cases worldwide and 30,000 fatalities. According to serological research by Henderson et al., West Nile virus (WNV), yellow fever virus (YFV), and zika virus (ZIKV) prevalence rates were 16.8% in Uganda [25].
Arbovirus-vector interactions
Vector competence:
The term "vector competence" describes an arthropod vector's capacity to acquire viral infection, sustain viral replication, and disseminate the virus to a susceptible host. Not all vectors are equally competent for all arboviruses, and this variation influences transmission dynamics [26].
Vector feeding behaviour:
Arbovirus transmission may be affected by a vector's feeding behaviour, including host selection and frequency. Some vectors prefer to feed on people, increasing the danger of human infections, whereas others have a wider host range [27].
5.3 Vector reproductive biology:
The reproductive biology of vectors, including breeding locations and reproduction rates, has an impact on vector populations and, as a result, the risk of arbovirus transmission. For control efforts, it is crucial that one understands vector ecology [6].
Vector immune responses:
Vector animals have developed immune systems that can restrict the reproduction of arboviruses. Understanding vector immune systems can help us better understand vector competence and potential treatment options [28].
Co-infections and competition:
In some cases, vectors can become co-infected with multiple arboviruses. Co-infections can lead to competition among the viruses within the vector, affecting transmission rates and the evolution of viral strains [29].
Environmental factors:
Temperature and humidity are only two examples of environmental variables that might have an impact on the survival, behaviour, and interactions of vectors with viruses. The epidemiology of arboviral illnesses can shift as a result of climate change, as can the spread of vectors [30].
Vector control strategies:
Understanding vector biology and interactions with arboviruses is crucial for the development of vector control strategies. These strategies may include insecticide use, habitat modification, and genetic manipulation of vectors to reduce their competence [31].
Historical of arboviruses
Aedes aegypti, also known as the yellow fever mosquito, constitutes one of the most frequent arbovirus vectors. This particular species may also spread dengue, chikungunya, zika, and Mayaro in addition to yellow fever. The range of A. aegypti significantly grew during the 15th and 19th centuries as a result of the African slave trade and growing globalisation. Throughout Asia, Africa, and North America in the 18th and 19th centuries, dengue fever epidemics remained a frequent effect of it.
It wasn't until 1881 that Carlos Finlay, a Cuban physician and scientist, proposed that insects rather than humans were the primary carrier of yellow fever, contrary to earlier theories. Major Walter Reed didn't validate the idea until 1901, almost 20 years later.
Five years later, in 1906, another significant finding was made about the propagation of dengue fever by A. aegypti, making dengue fever and yellow fever the first two illnesses recognised as being brought on by viruses. Then, in 1936 and 1937, respectively, the West Nile virus & tick-borne encephalitis were identified. Before 1970, just nine countries had significant dengue outbreaks, but the disease is now widespread in over 100 countries, reported to the World Health Organisation (WHO).
The Zika virus was initially identified in monkeys in 1947, and humans acquired the illness five years later. Zika's geographic distribution continued to expand during the ensuing decades, but no outbreaks and just 14 human instances of the infection were reported. Up to a significant outbreak on the Pacific Island of Yap in 2007 due to a lack of cases, the virus was not a major worry. on the years that followed, thorough studies were carried out into the significant outbreaks on four other Pacific Islands. After a significant epidemic in Brazil in 2015, cases of microcephaly—a birth condition in which the baby's head is significantly smaller than it should be—rose substantially. It was revealed shortly after the epidemic that Zika has been associated to an increase in microcephaly and other neurological abnormalities [32].
Historical perspective of arbovirus vaccine
The historical perspective of arbovirus vaccines is given in the table 2.
Table 2: Historical perspective of arbovirus vaccine
|
Vaccine
|
Historical development
|
Description
|
References
|
|
Yellow fever vaccine (YFV)
|
Max Theiler developed the live attenuated YFV in the 1930s.
|
It became the first arbovirus vaccine, preventing yellow fever in endemic regions.
|
[33]
|
|
Japanese encephalitis vaccine (JEV)
|
In the 1940s, the inactivated JEV was developed in Japan.
|
Inactivated and live attenuated JEV vaccines have been used to prevent Japanese encephalitis in endemic regions.
|
[34]
|
|
Tick-borne encephalitis vaccine (TBEV)
|
The inactivated TBEV vaccine was introduced in the 1940s in the former Soviet Union.
|
Preventing tick-borne encephalitis in Europe and Asia.
|
[35]
|
|
Dengue vaccine development (DVD)
|
Dengue vaccine development efforts spanned decades with the first licensed dengue vaccine, dengvaxia, becoming available in the late 2010s.
|
Challenges related to its efficacy and safety highlighted the complexity of dengue vaccine development.
|
[36]
|
Modern Approaches to Arbovirus Vaccine Development
The modern approaches to arbovirus vaccine development are given below;
Reverse genetics and synthetic biology:
The development of modern arbovirus vaccines frequently uses biotechnology and genetic modification methods. These techniques enable the modification of viral genomes to produce attenuated or inactivated vaccines [37].
mRNA vaccines:
A quick and adaptable technique for developing an arbovirus vaccine is provided by mRNA vaccine platforms, such as those utilised for COVID-19 vaccines. They permit the synthesis of viral antigens in host cells, resulting in a potent immunological response [38].
Viral vector vaccines:
Viral vector vaccines, such as those based on adenovirus or vesicular stomatitis virus (VSV) vectors, have shown promise for arbovirus vaccine development. They can deliver arbovirus antigens to the host’s immune system, inducing protective immunity [39].
Subunit vaccines:
Subunit vaccinations concentrate on particular viral proteins or epitopes. Compared to live vaccines, they are safer and more convenient to manufacture. Subunit vaccinations for arboviruses frequently target the envelope proteins necessary for viral entry [40].
Virus-like protein (VLP) vaccines:
VLP vaccines mimic the structure of intact viruses without containing genetic material, making them safe and effective for arbovirus vaccine candidates. They trigger strong antibody responses [41].
Structural biology and rational design:
Researchers are now able to comprehend the three-dimensional structures of arbovirus proteins because to developments in structural biology. This information supports the logical development of vaccinations that trigger protective immune responses [42].
Adjutants and immunomodulators:
Incorporating novel adjuvants and immunomodulators enhances the efficacy of arbovirus vaccines. These compounds stimulate the immune system, improving the vaccine's ability to generate protective immunity [43].
Clinical trials and vaccine candidates
The clinical trials and vaccine candidates are given in the table 3.
Table 3: Clinical trials and vaccine candidates
|
Vaccine candidate
|
Arbovirus
|
Clinical trials
|
References
|
|
Dengue vaccine
|
Dengue virus
|
Several clinical trials have been conducted for Dengue vaccine candidates, including CYD-TDV (Dengvaxia)
|
[44]
|
|
Zika vaccine
|
Zika virus
|
Candidates for the zika virus vaccine have undergone pre-clinical and early-stage clinical testing. Inactivated and DNA-based vaccinations have shown potential.
|
[45]
|
|
Chikungunya vaccine
|
Chikungunya virus
|
VLA1553, a chikungunya vaccine candidate, has entered clinical trials to evaluate its safety and efficacy.
|
[46]
|
|
West Nile vaccine
|
West Nile virus
|
Various West Nile virus vaccine candidates have been developed and tested in pre-clinical and clinical trials
|
[47]
|
|
Yellow fever vaccine
|
Yellow fever virus
|
Safety and immunogenicity studies of YF-17D vaccine
|
[48]
|
Challenges and Hurdles
Arboviruses, particularly ones like Dengue and Zika, exhibit substantial antigenic diversity with numerous serotypes or subtypes. It can be difficult to create vaccinations that offer extensive defence against these variations [7]. Arboviruses rely on vectors (like mosquitoes or ticks) for transmission. It is rare to eradicate this transmission cycle with vaccine, which necessitates concerted efforts in vector management and immunisation [17]. Pre-existing immunity from earlier arbovirus infections or vaccines may occasionally increase illness severity via antibody-dependent enhancement (ADE). The creation of vaccines must handle this challenge [49]. Arbovirus vaccine security must be ensured. Safety concerns regarding some vaccines, including Dengvaxia, highlight the necessity of meticulous testing, monitoring, and surveillance [50]. The uptake and use of the arbovirus vaccination could be hampered by vaccine reluctance and false information. It's crucial to establish trust and respond to public concerns [51].
Future directions and perspectives
Advanced vaccine platforms including mRNA vaccines, viral vectors, and delivery methods based on nanotechnology should be explored in further research. These platforms provide quick response times and improved immunogenicity [52]. The conception across all arbovirus vaccines that really can offer comprehensive defence against many serotypes and strains is a critical objective. The identification of conserved epitopes for these vaccines can be assisted by improvements in biological research [53]. It is important to continue pursuing integrated solutions that incorporate vaccination with vector control and surveillance techniques. These methods could support in preventing the spread of arboviruses [54]. Adopting a One Health strategy, which combines concerns for the health of people, animals, and the environment, can improve arbovirus monitoring and management. Collaboration helps reduce the likelihood of spillover incidents [55]. The community should be included in immunisation programmes, as well as behavioural treatments. Improving vaccine acceptance and coverage requires a clear understanding of human behaviour and perceptions [56]. For the study of arboviruses and the development of vaccines, it is crucial to improve worldwide cooperation, knowledge exchange, and resource allocation [57].
Conclusion
In the face of the ongoing threat posed by arboviruses, the development of new vaccines represents a beacon of hope for global public health. The diverse array of arboviruses, each with its unique challenges and complexities, has necessitated innovative approaches and a comprehensive strategy. The potential of next-generation vaccine platforms, such as mRNA vaccines and viral vectors, offers exciting opportunities for rapid response and broader protection against arboviruses. These platforms, driven by advances in science and technology, provide a path toward the development of vaccines capable of tackling the antigenic diversity inherent to arboviruses. The quest for universal arbovirus vaccines, capable of conferring cross-protection against multiple serotypes and strains, is a goal that remains within reach. Structural biology has shed light on conserved epitopes, serving as promising targets for the design of such vaccines. Furthermore, a holistic approach is required. Combining vaccination with vector control, surveillance, and a One Health perspective is essential to interrupt the transmission cycle of arboviruses. Behavioural interventions and community engagement are integral components, as understanding human behaviour and perceptions is central to achieving high vaccine coverage. In this endeavour, global collaboration and resource allocation are paramount. Governments, academia, industry, and international organizations must unite their efforts to overcome the multifaceted challenge of arboviral diseases. In conclusion, while arboviruses continue to threaten populations worldwide, the ongoing research and development of new vaccines provide reasons for optimism. Through innovation, interdisciplinary collaboration, and a shared commitment to global health security, we can chart a course toward a world less vulnerable to the ravages of arboviral diseases, ensuring a safer and healthier future for all.
