Bamboo stumps that are artificially in use put pressure on dengue and chikungunya vector control in Dhaka city, Bangladesh.

BACKGROUND OBJECTIVES: Aedes aegypti and Ae. albopictus mosquitoes breed in natural and artificial containers, and they transmit dengue and chikungunya. A study was conducted to identify the contribution of bamboo stumps to these disease vectors that were used in the flower garden as pillars to hold the bamboo flex fence. METHODS: Two sizes of whole bamboo were used to hold fences around gardens at Dhaka University, Bangladesh, and were painted red and green. Mosquito larvae and pupae were collected from bamboo stumps between July and August, and vectors were identified up to the species level. The data were analyzed using the STATA/MP 14.2 version. RESULTS: 83.5% and 0.2% were Ae. albopictus and Ae. aegypti, respectively, and the remaining were Culex and Ar-migeres species. Ae. albopictus, Ae. aegypti, and both species-positive bamboo stumps were 46.9, 0.7, and 47.1%, respectively. 54.5% of the bamboo stumps had at least one mosquito species. The average stump depth for Aedes positive stumps (mean=11.7 cm, SE = 0.5) was significantly (p <0.001) higher than the Aedes negative stumps (mean = 9.5 cm, SE = 0.4). 53.8% and 38.0% stumps were found Aedes positive on the ground and upper sides of fences, respectively, and found significant (p<0.01) differences between both sides. A zero-inflated negative binomial count model is significant at a 5% level of significance, χ2(4) = 11.8, p = 0.019 (<0.05) for Ae. albopictus. Stump depth is found to have a significant positive effect on the number of Aedes-positive stumps. INTERPRETATION CONCLUSION: Artificially used natural containers are adding pressure to current mosquito control activities as mosquitoes are breeding on them, which needs additional attention.

[Dengue, chikungunya and the mosquito vector at the Southern limit of distribution during the 2023 epidemic, Argentina]. / Dengue, chikungunya y el mosquito vector en el límite sur de distribución durante la epidemia 2023, Argentina.

OBJECTIVES: To monitor the oviposition activity of the mosquito Aedes aegypti and of dengue and chikungunya cases in four localities of temperate Argentina, during the 2023 epidemic. METHODS: During the summer and autumn of 2023, the oviposition activity of the mosquito vector was monitored weekly using ovitraps, and the arrival of cases with dengue or chikungunya in Tandil, Olavarría, Bahía Blanca and Laprida were registered. RESULTS: Monthly variations of the percentage of positive traps were similar in the first three locations; in Laprida the mosquito was not detected. On the contrary, a significant difference was observed in the percentage of total traps that ever tested positive in each locality, being higher in Olavarría (83.3%) than in Bahía Blanca (68.6%) and Tandil (48.7%). Regarding diseases, 18 imported cases of dengue and 3 of chikungunya were registered. In addition, the first autochthonous case of dengue in the region was recorded, being the southernmost until known. CONCLUSION: It is essential to raise awareness and train the members of the health systems of the new regions exposed to Ae. aegypti for early detection of cases, and to the general population to enhance prevention actions.

OBJETIVOS: Monitorear la actividad de oviposición del mosquito Aedes aegypti y de casos de dengue y chikungunya en cuatro localidades de Argentina templada, durante la epidemia del 2023. Métodos: Durante el verano y otoño del 2023, se monitoreó semanalmente mediante ovitrampas la actividad de oviposición del mosquito vector, y se registró el arribo de casos con dengue o chikungunya a Tandil, Olavarría, Bahía Blanca y Laprida. RESULTADOS: La variación mensual del porcentaje de trampas positivas fue similar en las tres primeras localidades; en Laprida no se detectó el mosquito. Por el contrario, se observó una diferencia significativa del porcentaje de trampas que alguna vez resultó positiva en cada localidad, siendo mayor en Olavarría (83%), que en Bahía Blanca (67%) y Tandil (49%). Respecto a las enfermedades, se registraron 18 casos importados de dengue y 3 de chikungunya. Además, se registró el primer caso autóctono de dengue en la región, siendo el más austral hasta el momento. Conclusión: Es imprescindible sensibilizar y capacitar a los integrantes de los sistemas de salud de las nuevas regiones expuestas al Ae. aegypti para la detección temprana de casos, y a la población en general para potenciar las acciones de prevención.

Programmatic considerations and evidence gaps for chikungunya vaccine introduction in countries at risk of chikungunya outbreaks: Stakeholder analysis.

Chikungunya can have longstanding effects on health and quality of life. Alongside the recent approval of the world's first chikungunya vaccine by the US Food and Drug Administration in November 2023 and with new chikungunya vaccines in the pipeline, it is important to understand the perspectives of stakeholders before vaccine rollout. Our study aim is to identify key programmatic considerations and gaps in Evidence-to-Recommendation criteria for chikungunya vaccine introduction. We used purposive and snowball sampling to identify global, national, and subnational stakeholders from outbreak prone areas, including Latin America, Asia, and Africa. Semi-structured in-depth interviews were conducted and analysed using qualitative descriptive methods. We found that perspectives varied between tiers of stakeholders and geographies. Unknown disease burden, diagnostics, non-specific disease surveillance, undefined target populations for vaccination, and low disease prioritisation were critical challenges identified by stakeholders that need to be addressed to facilitate rolling out a chikungunya vaccine. Future investments should address these challenges to generate useful evidence for decision-making on new chikungunya vaccine introduction.

Live-attenuated CHIKV vaccine with rearranged genome replicates in vitro and induces immune response in mice.

Chikungunya fever virus (CHIKV) is a mosquito-borne alphavirus that causes wide-spread human infections and epidemics in Asia, Africa and recently, in the Americas. CHIKV is considered a priority pathogen by CEPI and WHO. Despite recent approval of a live-attenuated CHIKV vaccine, development of additional vaccines is warranted due to the worldwide outbreaks of CHIKV. Previously, we developed immunization DNA (iDNA) plasmid capable of launching live-attenuated CHIKV vaccine in vivo. Here we report the use of CHIKV iDNA plasmid to prepare a novel, live-attenuated CHIKV vaccine V5040 with rearranged RNA genome. In V5040, genomic RNA was rearranged to encode capsid gene downstream from the glycoprotein genes. Attenuated mutations derived from experimental CHIKV 181/25 vaccine were also engineered into E2 gene of V5040. The DNA copy of rearranged CHIKV genomic RNA with attenuated mutations was cloned into iDNA plasmid pMG5040 downstream from the CMV promoter. After transfection in vitro, pMG5040 launched replication of V5040 virus with rearranged genome and attenuating E2 mutations. Furthermore, V5040 virus was evaluated in experimental murine models for general safety and immunogenicity. Vaccination with V5040 virus subcutaneously resulted in elicitation of CHIKV-specific, virus-neutralizing antibodies. The results warrant further evaluation of V5040 virus with rearranged genome as a novel live-attenuated vaccine for CHIKV.

A Divalent Chikungunya and Zika Nanovaccine with Thermostable Self-Assembly Multivalent Scaffold LS-SUMO.

The convergence strategies of antigenic subunits and synthetic nanoparticle scaffold platform improve the vaccine production efficiency and enhance vaccine-induced immunogenicity. Selecting the appropriate nanoparticle scaffold is crucial to controlling target antigens immunologically. Lumazine synthase (LS) is an attractive candidate for a vaccine display system due to its thermostability, modification tolerance, and morphological plasticity. Here, the first development of a multivalent thermostable scaffold, LS-SUMO (SUMO, small ubiquitin-likemodifier), and a divalent nanovaccine covalently conjugated with Chikungunya virus E2 and Zika virus EDIII antigens, is reported. Compared with antigen monomers, LS-SUMO nanoparticle vaccines elicit a higher humoral response and neutralizing antibodies against both antigen targets in mouse sera. Mice immunized with LS-SUMO conjugates produce CD4+ T cell-mediated Th2-biased responses and promote humoral immunity. Importantly, LS-SUMO conjugates possess equivalent humoral immunogenicity after heat treatment. Taken together, LS-SUMO is a powerful biotargeting nanoplatform with high-yield production, thermal stability and opens a new avenue for multivalent presentation of various antigens.

Immunogenicity, safety and duration of protection afforded by chikungunya virus vaccines undergoing human clinical trials.

Background. Chikungunya virus (CHIKV) causes chikungunya fever and has been responsible for major global epidemics of arthritic disease over the past two decades. Multiple CHIKV vaccine candidates are currently undergoing or have undergone human clinical trials, with one vaccine candidate receiving FDA approval. This scoping review was performed to evaluate the 'efficacy', 'safety' and 'duration of protection' provided by CHIKV vaccine candidates in human clinical trials.Methods. This scoping literature review addresses studies involving CHIKV vaccine clinical trials using available literature on the PubMed, Medline Embase, Cochrane Library and Clinicaltrial.gov databases published up to 25 August 2023. Covidence software was used to structure information and review the studies included in this article.Results. A total of 1138 studies were screened and, after removal of duplicate studies, 12 relevant studies were thoroughly reviewed to gather information. This review summarizs that all seven CHIKV vaccine candidates achieved over 90 % seroprotection against CHIKV after one or two doses. All vaccines were able to provide neutralizing antibody protection for at least 28 days.Conclusions. A variety of vaccine technologies have been used to develop CHIKV vaccine candidates. With one vaccine candidate having recently received FDA approval, it is likely that further CHIKV vaccines will be available commercially in the near future.

A randomized, double-blinded Phase 3 study to demonstrate lot-to-lot consistency and to confirm immunogenicity and safety of the live-attenuated chikungunya virus vaccine candidate VLA1553 in healthy adults†.

BACKGROUND: The global spread of the chikungunya virus (CHIKV) increases the exposure risk for individuals travelling to or living in endemic areas. This Phase 3 study was designed to demonstrate manufacturing consistency between three lots of the single shot live-attenuated CHIKV vaccine VLA1553, and to confirm the promising immunogenicity and safety data obtained in previous trials. METHODS: This randomized, double-blinded, lot-to-lot consistency, Phase 3 study, assessed immunogenicity and safety of VLA1553 in 408 healthy adults (18-45 years) in 12 sites across the USA. The primary endpoint was a comparison of the geometric mean titre (GMT) ratios of CHIKV-specific neutralizing antibodies between three VLA1553 lots at 28 days post-vaccination. Secondary endpoints included immunogenicity and safety over 6 months post-vaccination. RESULTS: GMTs were comparable between the lots meeting the acceptance criteria for equivalence. The average GMT (measured by 50% CHIKV micro plaque neutralization test; µPRNT50) peaked with 2643 at 28 days post-vaccination and decreased to 709 at 6 months post-vaccination. An excellent seroresponse rate (defined as µPRNT50 titre ≥ 150 considered protective) was achieved in 97.8% of participants at 28 days post-vaccination and still persisted in 96% at 6 months after vaccination. Upon VLA1553 immunization, 72.5% of participants experienced adverse events (AEs), without significant differences between lots (related solicited systemic AE: 53.9% of participants; related solicited local AE: 19.4%). Overall, AEs were mostly mild or moderate and resolved without sequela, usually within 3 days. With 3.9% of participants experiencing severe AEs, 2.7% were classified as related, whereas none of the six reported serious adverse events was related to the administration of VLA1553. CONCLUSIONS: All three lots of VLA1553 recapitulated the safety and immunogenicity profiles of a preceding Phase 3 study, fulfilling pre-defined consistency requirements. These results highlight the manufacturability of VLA1553, a promising vaccine for the prevention of CHIKV disease for those living in or travelling to endemic areas.

Rational design of a multivalent vaccine targeting arthropod-borne viruses using reverse vaccinology strategies.

Viruses transmitted by arthropods, such as Dengue, Zika, and Chikungunya, represent substantial worldwide health threats, particularly in countries like India. The lack of approved vaccines and effective antiviral therapies calls for developing innovative strategies to tackle these arboviruses. In this study, we employed immunoinformatics methodologies, incorporating reverse vaccinology, to design a multivalent vaccine targeting the predominant arboviruses. Epitopes of B and T cells were recognized within the non-structural proteins of Dengue, Zika, and Chikungunya viruses. The predicted epitopes were enhanced with adjuvants ß-defensin and RS-09 to boost the vaccine's immunogenicity. Sixteen distinct vaccine candidates were constructed, each incorporating epitopes from all three viruses. FUVAC-11 emerged as the most promising vaccine candidate through molecular docking and molecular dynamics simulations, demonstrating favorable binding interactions and stability. Its effectiveness was further evaluated using computational immunological studies confirming strong immune responses. The in silico cloning performed using the pET-28a(+) plasmid facilitates the future experimental implementation of this vaccine candidate, paving the way for potential advancements in combating these significant arboviral threats. However, further in vitro and in vivo studies are warranted to confirm the results obtained in this computational study, which highlights the effectiveness of immunoinformatics and reverse vaccinology in creating vaccines against major Arboviruses, offering a promising model for developing vaccines for other vector-borne diseases and enhancing global health security.

Entomopathogenic fungi for the control of larvae and adults of Aedes aegypti (Diptera: Culicidae) vector of dengue, chikungunya and Zika viruses in Mexico.

OBJECTIVE: To assess larvicide and adulticide activity of different native strains of fungi on Aedes aegypti. MATERIALS AND METHODS: Third instar larvae were exposed for 72 h at a concentration of 1x108 conidia/ml of 15 fungi; only fungi that significantly affected the larvae were evaluated against the adult phase at a concentration of 2x1010 conidia/ml. Mortality readings were performed at 24, 48, and 72 h for larvae, and every day to 30 days for adults. RESULTS: Trichoderma longibrachiatum, Aspergillus aculeatus, and Metarhizium anisopliae had the best larvicidal activity at 24 h of exposure (p<0.05), causing mortalities of 100, 72, and 62%, respectively. Adult mosquitoes were more affected by Gliocladium virens (45% mortality), M. anisopliae (30% mortality), and T. longibrachiatum (23.33% mortality). CONCLUSION: The larval stage of Ae. aegypti was more susceptible than the adult phase to the pathogenic action of native fungi, with T. longibrachiatum being with the highest virulence.

A chikungunya vaccine is likely to get approved. Who will get it?

Travelers are first, but the real need is in endemic areas.

FHL1 promotes chikungunya and o'nyong-nyong virus infection and pathogenesis with implications for alphavirus vaccine design.

Arthritogenic alphaviruses are positive-strand RNA viruses that cause debilitating musculoskeletal diseases affecting millions worldwide. A recent discovery identified the four-and-a-half-LIM domain protein 1 splice variant A (FHL1A) as a crucial host factor interacting with the hypervariable domain (HVD) of chikungunya virus (CHIKV) nonstructural protein 3 (nsP3). Here, we show that acute and chronic chikungunya disease in humans correlates with elevated levels of FHL1. We generated FHL1-/- mice, which when infected with CHIKV or o'nyong-nyong virus (ONNV) displayed reduced arthritis and myositis, fewer immune infiltrates, and reduced proinflammatory cytokine/chemokine outputs, compared to infected wild-type (WT) mice. Interestingly, disease signs were comparable in FHL1-/- and WT mice infected with arthritogenic alphaviruses Ross River virus (RRV) or Mayaro virus (MAYV). This aligns with pull-down assay data, which showed the ability of CHIKV and ONNV nsP3 to interact with FHL1, while RRV and MAYV nsP3s did not. We engineered a CHIKV mutant unable to bind FHL1 (CHIKV-ΔFHL1), which was avirulent in vivo. Following inoculation with CHIKV-ΔFHL1, mice were protected from disease upon challenge with CHIKV and ONNV, and viraemia was significantly reduced in RRV- and MAYV-challenged mice. Targeting FHL1-binding as an approach to vaccine design could lead to breakthroughs in mitigating alphaviral disease.

Analysis of the dynamics of a vector-borne infection with the effect of imperfect vaccination from a fractional perspective.

The burden of vector-borne infections is significant, particularly in low- and middle-income countries where vector populations are high and healthcare infrastructure may be inadequate. Further, studies are required to investigate the key factors of vector-borne infections to provide effective control measure. This study focuses on formulating a mathematical framework to characterize the spread of chikungunya infection in the presence of vaccines and treatments. The research is primarily dedicated to descriptive study and comprehension of dynamic behaviour of chikungunya dynamics. We use Banach's and Schaefer's fixed point theorems to investigate the existence and uniqueness of the suggested chikungunya framework resolution. Additionally, we confirm the Ulam-Hyers stability of the chikungunya system. To assess the impact of various parameters on the dynamics of chikungunya, we examine solution pathways using the Laplace-Adomian method of disintegration. Specifically, to visualise the impacts of fractional order, vaccination, bite rate and treatment computer algorithms are employed on the infection level of chikungunya. Our research identified the framework's essential input settings for managing chikungunya infection. Notably, the intensity of chikungunya infection can be reduced by lowering mosquito bite rates in the affected area. On the other hand, vaccination, memory index or fractional order, and treatment could be used as efficient controlling variables.

A measles virus-based vaccine induces robust chikungunya virus-specific CD4+ T-cell responses in a phase II clinical trial.

Chikungunya virus (CHIKV) is an alphavirus transmitted by mosquitos that causes a debilitating disease characterized by fever and long-lasting polyarthralgia. To date, no vaccine has been licensed, but multiple vaccine candidates are under evaluation in clinical trials. One of these vaccines is based on a measles virus vector encoding for the CHIKV structural genes C, E3, E2, 6K, and E1 (MV-CHIK), which proved safe in phase I and II clinical trials and elicited CHIKV-specific antibody responses in adult measles seropositive vaccine recipients. Here, we predicted T-cell epitopes in the CHIKV structural genes and investigated whether MV-CHIK vaccination induced CHIKV-specific CD4+ and/or CD8+ T-cell responses. Immune-dominant regions containing multiple epitopes in silico predicted to bind to HLA class II molecules were found for four of the five structural proteins, while no such regions were predicted for HLA class I. Experimentally, CHIKV-specific CD4+ T-cells were detected in six out of twelve participants after a single MV-CHIK vaccination and more robust responses were found 4 weeks after two vaccinations (ten out of twelve participants). T-cells were mainly directed against the three large structural proteins C, E2 and E1. Next, we sorted and expanded CHIKV-specific T cell clones (TCC) and identified human CHIKV T-cell epitopes by deconvolution. Interestingly, eight out of nine CD4+ TCC recognized an epitope in accordance with the in silico prediction. CHIKV-specific CD8+ T-cells induced by MV-CHIK vaccination were inconsistently detected. Our data show that the MV-CHIK vector vaccine induced a functional transgene-specific CD4+ T cell response which, together with the evidence of neutralizing antibodies as correlate of protection for CHIKV, makes MV-CHIK a promising vaccine candidate in the prevention of chikungunya.