Mosquito Salivary Proteins and Arbovirus Infection: From Viral Enhancers to Potential Targets for Vaccines

Arthropod-borne viruses present important public health challenges worldwide. Viruses such as DENV, ZIKV, and WNV are of current concern due to an increasing incidence and an expanding geographic range, generating explosive outbreaks even in non-endemic areas. The clinical signs associated with infection from these arboviruses are often inapparent, mild, or nonspecific, but occasionally develop into serious complications marked by rapid onset, tremors, paralysis, hemorrhagic fever, neurological alterations, or death. They are predominately transmitted to humans through mosquito bite, during which saliva is inoculated into the skin to facilitate blood feeding. A new approach to prevent arboviral diseases has been proposed by the observation that arthropod saliva facilitates transmission of pathogens. Viruses released within mosquito saliva may more easily initiate host invasion by taking advantage of the host’s innate and adaptive immune responses to saliva. This provides a rationale for creating vaccines against mosquito salivary proteins, especially because of the lack of licensed vaccines against most of these viruses. This review aims to provide an overview of the effects on the host immune response by the mosquito salivary proteins and how these phenomena alter the infection outcome for different arboviruses, recent attempts to generate mosquito salivary-based vaccines against flavivirus including DENV, ZIKV, and WNV, and the potential benefits and pitfalls that this strategy involves.

• Publication year

  2023

• Venue

  Pathogens

• Publication date

  2023-02-23

• Fields of study

  Biology, Medicine, Environmental Science

• Identifiers
  DOI 10.3390/pathogens12030371PMID 36986293PMCID 10054260
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Safety and immunogenicity of AGS-v PLUS, a mosquito saliva peptide vaccine against arboviral diseases: A randomized, double-blind, placebo-controlled Phase 1 trial

  2022cited by this paper
• Aedes aegypti sialokinin facilitates mosquito blood feeding and modulates host immunity and vascular biology.

  2022cited by this paper
• Mosquito saliva enhances virus infection through sialokinin-dependent vascular leakage

  2022cited by this paper
• Aedes aegypti anti-salivary proteins IgG levels in a cohort of DENV-like symptoms subjects from a dengue-endemic region in Colombia

  2022cited by this paper
• Human IgG responses to the Aedes albopictus 34k2 salivary protein: analyses in Réunion Island and Bolivia confirm its suitability as marker of host exposure to the tiger mosquito

  2022cited by this paper
• Development of inapparent dengue associated with increased antibody levels to Aedes aegypti salivary proteins: a longitudinal dengue cohort in Cambodia.

  2021cited by this paper
• Enhancement of Zika virus infection by antibodies from West Nile virus seropositive individuals with no history of clinical infection

  2021cited by this paper
• AgBR1 and NeSt1 antisera protect mice from Aedes aegypti-borne Zika infection.

  2021cited by this paper
• A 20-year historical review of West Nile virus since its initial emergence in North America: Has West Nile virus become a neglected tropical disease?

  2021cited by this paper
• Serological biomarker for assessing human exposure to Aedes mosquito bites during a randomized vector control intervention trial in northeastern Thailand

  2021cited by this paper
• Aedes albopictus D7 Salivary Protein Prevents Host Hemostasis and Inflammation

  2020cited by this paper
• A mosquito salivary protein promotes flavivirus transmission by activation of autophagy

  2020cited by this paper
• Identification and Pilot Evaluation of Salivary Peptides from Anopheles albimanus as Biomarkers for Bite Exposure and Malaria Infection in Colombia

  2020cited by this paper
• Vaccination with Aedes aegypti AgBR1 Delays Lethal Mosquito-Borne Zika Virus Infection in Mice

  2020cited by this paper
• ADP binding by the Culex quinquefasciatus mosquito D7 salivary protein enhances blood feeding on mammals

  2020cited by this paper
• Safety and immunogenicity of a mosquito saliva peptide-based vaccine: a randomised, placebo-controlled, double-blind, phase 1 trial.

  2020cited by this paper
• Japanese Encephalitis Vaccines

  2020cited by this paper
• AgBR1 antibodies delay lethal Aedes aegypti-borne West Nile virus infection in mice

  2019cited by this paper
• Anopheline antiplatelet protein from mosquito saliva regulates blood feeding behavior

  2019cited by this paper
• First FDA-approved vaccine for the prevention of dengue disease in endemic regions

  2019cited by this paper
• Aedes aegypti AgBR1 antibodies modulate early Zika virus infection of mice

  2019influential reference
• Zika virus outbreak

  2019cited by this paper
• Aedes aegypti NeSt1 Protein Enhances Zika Virus Pathogenesis by Activating Neutrophils

  2019cited by this paper
• Human exposure to Anopheles farauti bites in the Solomon Islands is not associated with IgG antibody response to the gSG6 salivary protein of Anopheles gambiae

  2019cited by this paper
• Zika Virus Vaccine Development: Progress in the Face of New Challenges.

  2019cited by this paper
• A review of Dengvaxia®: development to deployment

  2019cited by this paper
• Analysis in a murine model points to IgG responses against the 34k2 salivary proteins from Aedes albopictus and Aedes aegypti as novel promising candidate markers of host exposure to Aedes mosquitoes

  2019cited by this paper
• Increased Mosquito Midgut Infection by Dengue Virus Recruitment of Plasmin Is Blocked by an Endogenous Kazal-type Inhibitor

  2019cited by this paper
• A salivary protein of Aedes aegypti promotes dengue-2 virus replication and transmission.

  2019cited by this paper
• Zika Virus Vaccine: Progress and Challenges.

  2018cited by this paper
• Salivary factor LTRIN from Aedes aegypti facilitates the transmission of Zika virus by interfering with the lymphotoxin-β receptor

  2018cited by this paper
• Mosquito Saliva Reshapes Alphavirus Infection and Immunopathogenesis

  2018cited by this paper
• Salivary factor LTRIN from Aedes aegypti facilitates the transmission of Zika virus by interfering with the lymphotoxin-β receptor

  2018cited by this paper
• Serosurvey of Human Antibodies Recognizing Aedes aegypti D7 Salivary Proteins in Colombia

  2018cited by this paper
• Mosquito saliva alone has profound effects on the human immune system

  2018cited by this paper
• New Immuno-Epidemiological Biomarker of Human Exposure to Aedes Vector Bites: From Concept to Applications †

  2018cited by this paper
• Flavivirus Pathogenesis in the Mosquito Transmission Vector

  2017cited by this paper
• Live Attenuated Yellow Fever 17D Vaccine: A Legacy Vaccine Still Controlling Outbreaks In Modern Day

  2017cited by this paper
• Enhancement of Zika virus pathogenesis by preexisting antiflavivirus immunity

  2017cited by this paper
• Recent advances in human flavivirus vaccines.

  2017cited by this paper
• Zika virus genome from the Americas.

  2016cited by this paper
• Host Inflammatory Response to Mosquito Bites Enhances the Severity of Arbovirus Infection

  2016cited by this paper
• Mosquito Saliva Increases Endothelial Permeability in the Skin, Immune Cell Migration, and Dengue Pathogenesis during Antibody-Dependent Enhancement

  2016influential reference
• Zika Virus Spreads to New Areas - Region of the Americas, May 2015-January 2016.

  2016cited by this paper
• Arbovirosis and potential transmission blocking vaccines

  2016cited by this paper
• Operational Assessment of Long-Lasting Insecticidal Nets by Using an Anopheles Salivary Biomarker of Human-Vector Contact.

  2016cited by this paper
• Aedes aegypti D7 Saliva Protein Inhibits Dengue Virus Infection

  2016cited by this paper
• Climate change influences on global distributions of dengue and chikungunya virus vectors

  2015cited by this paper
• From the Centers for Disease Control and Prevention

  2015cited by this paper
• Parameters of Mosquito-Enhanced West Nile Virus Infection

  2015cited by this paper
• Dengue Virus Infection of Aedes aegypti Requires a Putative Cysteine Rich Venom Protein

  2015cited by this paper
• Zika Virus Outbreak, Bahia, Brazil

  2015cited by this paper
• Aedes aegypti salivary protein "aegyptin" co-inoculation modulates dengue virus infection in the vertebrate host.

  2014cited by this paper
• Differential antibody response to the Anopheles gambiae gSG6 and cE5 salivary proteins in individuals naturally exposed to bites of malaria vectors

  2014cited by this paper
• Collagen-binding protein, Aegyptin, regulates probing time and blood feeding success in the dengue vector mosquito, Aedes aegypti

  2014cited by this paper
• Aedes aegypti saliva contains a prominent 34-kDa protein that strongly enhances dengue virus replication in human keratinocytes.

  2014cited by this paper
• Secondary infection as a risk factor for dengue hemorrhagic fever/dengue shock syndrome: an historical perspective and role of antibody-dependent enhancement of infection

  2013cited by this paper
• Japanese encephalitis

  2013cited by this paper
• Mosquito Saliva Serine Protease Enhances Dissemination of Dengue Virus into the Mammalian Host

  2013cited by this paper
• The global distribution and burden of dengue

  2013cited by this paper
• Aedes Mosquito Saliva Modulates Rift Valley Fever Virus Pathogenicity

  2013cited by this paper
• Immunization with Culex tarsalis Mosquito Salivary Gland Extract Modulates West Nile Virus Infection and Disease in Mice

  2013cited by this paper
• Immune evasion strategies of flaviviruses.

  2013cited by this paper
• Human Antibody Response to Anopheles Saliva for Comparing the Efficacy of Three Malaria Vector Control Methods in Balombo, Angola

  2012cited by this paper
• The Immune Response to Sand Fly Salivary Proteins and Its Influence on Leishmania Immunity

  2012cited by this paper
• Human antibody response to Aedes aegypti saliva in an urban population in Bolivia: a new biomarker of exposure to Dengue vector bites.

  2012cited by this paper
• Association of human immune response to Aedes aegypti salivary proteins with dengue disease severity

  2012cited by this paper
• Mosquito Bite Delivery of Dengue Virus Enhances Immunogenicity and Pathogenesis in Humanized Mice

  2012cited by this paper
• Unique thrombin inhibition mechanism by anophelin, an anticoagulant from the malaria vector

  2012cited by this paper
• Assessment of Anopheles salivary antigens as individual exposure biomarkers to species-specific malaria vector bites

  2012cited by this paper
• Immunization of Mice with Recombinant Mosquito Salivary Protein D7 Enhances Mortality from Subsequent West Nile Virus Infection via Mosquito Bite

  2012cited by this paper
• In-Depth Analysis of the Antibody Response of Individuals Exposed to Primary Dengue Virus Infection

  2011cited by this paper
• A tick mannose-binding lectin inhibitor interferes with the vertebrate complement cascade to enhance transmission of the lyme disease agent.

  2011cited by this paper
• Reporting rates of yellow fever vaccine 17D or 17DD-associated serious adverse events in pharmacovigilance data bases: systematic review.

  2011cited by this paper
• Japanese Encephalitis Vaccines.

  2011cited by this paper
• Dengue, Urbanization and Globalization: The Unholy Trinity of the 21st Century

  2011cited by this paper
• Aedes aegypti Saliva Alters Leukocyte Recruitment and Cytokine Signaling by Antigen-Presenting Cells during West Nile Virus Infection

  2010cited by this paper
• Phylogeography of West Nile Virus: from the Cradle of Evolution in Africa to Eurasia, Australia, and the Americas

  2010cited by this paper
• An insight into the sialome of blood-feeding Nematocera.

  2010cited by this paper
• Blood‐feeding and immunogenic Aedes aegypti saliva proteins

  2010cited by this paper
• Aegyptin displays high‐affinity for the von Willebrand factor binding site (RGQOGVMGF) in collagen and inhibits carotid thrombus formation in vivo

  2010cited by this paper
• Zika virus outbreak on Yap Island, Federated States of Micronesia.

  2009cited by this paper
• Yellow fever vaccine - how does it work and why do rare cases of serious adverse events take place?

  2009cited by this paper
• Inhibition of collagen-induced platelet aggregation by anopheline antiplatelet protein, a saliva protein from a malaria vector mosquito.

  2008cited by this paper
• Aegyptin, a Novel Mosquito Salivary Gland Protein, Specifically Binds to Collagen and Prevents Its Interaction with Platelet Glycoprotein VI, Integrin α2β1, and von Willebrand Factor*

  2007cited by this paper
• Identification and characterization of a new kallikrein-kinin system inhibitor from the salivary glands of the malaria vector mosquito Anopheles stephensi.

  2007cited by this paper
• An annotated catalogue of salivary gland transcripts in the adult female mosquito, Ædes ægypti*

  2007cited by this paper
• An insight into the sialome of the adult female mosquito Aedes albopictus.

  2007cited by this paper
• A novel secreted endonuclease from Culex quinquefasciatus salivary glands

  2006cited by this paper
• West Nile virus meningoencephalitis

  2006cited by this paper
• Function and Evolution of a Mosquito Salivary Protein Family*

  2006cited by this paper
• Expression of functional recombinant mosquito salivary apyrase: A potential therapeutic platelet aggregation inhibitor

  2006cited by this paper
• Differential modulation of murine host immune response by salivary gland extracts from the mosquitoes Aedes aegypti and Culex quinquefasciatus

  2004cited by this paper
• West Nile virus: where are we now?

  2004cited by this paper
• An insight into the salivary transcriptome and proteome of the adult female mosquito Culex pipiens quinquefasciatus.

  2004cited by this paper
• The salivary purine nucleosidase of the mosquito, Aedes aegypti.

  2003cited by this paper
• The D7 family of salivary proteins in blood sucking diptera

  2002cited by this paper
• A Mosquito Salivary Protein Inhibits Activation of the Plasma Contact System by Binding to Factor XII and High Molecular Weight Kininogen*

  2002cited by this paper
• Toward a description of the sialome of the adult female mosquito Aedes aegypti.

  2002cited by this paper
• Adenosine and inosine increase cutaneous vasopermeability by activating A(3) receptors on mast cells.

  2000cited by this paper

• Immunosuppressive impact of Aedes triseriatus salivary gland extract on lymphocyte biology

  2026cites this paper
• From promise to pitfalls: immunological lessons from dengue vaccines and their implications.

  2026cites this paper
• Insect-specific virus platforms for arbovirus vaccine development

  2025cites this paper
• Virus-like particle-based vaccines targeting the Anopheles mosquito salivary protein TRIO

  2025cites this paper
• From Bite to Brain: Arboviral Neuropathogenesis.

  2025cites this paper
• Repeated exposure to 31 kDa protein fraction from the salivary gland of Aedes aegypti modulate humoral and cellular immune response in mouse model.

  2025cites this paper
• Sphingomyelins in mosquito saliva reconfigure skin lipidome to promote viral protein levels and enhance transmission of flaviviruses.

  2025cites this paper
• Characterization of Mosquito Salivary Components.

  2025cites this paper
• AGS-v PLUS, a Mosquito Salivary Peptide Vaccine, Modulates the Response to Aedes Mosquito Bites in Humans

  2025cites this paper
• Antibodies to Female Aedes albopictus Salivary Proteins Promote Dengue Virus Infection with Salivary proteins

  2025cites this paper
• Molecular Docking of Interaction between D7 Protein from the Salivary Gland of Aedes aegypti and Leukotriene A4 for Developing Thrombolytic Agent

  2024cites this paper
• Efficacy and immunogenicity following dengue virus-1 human challenge after a tetravalent prime-boost dengue vaccine regimen: an open-label, phase 1 trial.

  2024cites this paper
• Fibrinopeptide A-induced blood-feeding arrest in the yellow fever mosquito Aedes aegypti.

  2024cites this paper
• Kemampuan Ikan Black Skirt Tetra (Gymnocorymbus Ternetzi) Memangsa Larva Aedes Aegypti

  2024cites this paper
• Extrinsic and intrinsic regulation of blood feeding in mosquitoes.

  2024cites this paper
• Virus-like particle-based vaccines targeting the Anopheles mosquito salivary protein, TRIO

  2024cites this paper
• Research progress toward arthropod salivary protein vaccine development for vector-borne infectious diseases

  2024cites this paper
• Peptides with Antimicrobial Activity in the Saliva of the Malaria Vector Anopheles coluzzii

  2024cites this paper
• Immunological and Pharmacological Potential of the Mosquito Sialome

  year unknowncites this paper