Can Vaccination cure dengue?

Dengue virus (DENV) has become the most frequent viral disease caused to humans due to the bite of infected mosquitoes. The disease has been transmitted rapidly in recent decades. Dengue virus has four serotypes (DENV 1, 2, 3, and 4), with a fifth identified in 2013. According to a statistical assessment conducted in dengue-prone endemic areas, 70-90 % of people can become infected with at least one DENV serotype by reaching puberty. Aedes mosquitoes transmit all dengue viruses. Dengue symptoms include severe fever, headache, eye pain, myalgia, arthralgia, rash, leukopenia, and nausea. Other than supportive care and preserving personal hygiene, there is no treatment available for Dengue at present. As a result, developing a safe dengue vaccine that provides long-term protection against all four DENV strains is high priority research globally. Dengue fever causes morbidity and mortality, which can be reduced through Vaccination. Let us know more about the vaccines developed or under development for treating Dengue that answers our headline.

Dengvaxia: The first Dengue vaccine by Sanofi Pasteur

Dengvaxia (short name as CYD-TDV) is the first dengue vaccine approved by WHO that is indicated to prevent dengue disease caused by the four serotypes of Dengue, namely DENV-1, DENV-2, DENV-3, and DENV-4. It is a live recombinant tetravalent vaccine available as a suspension for injection developed by Sanofi Pasteur. At present, Dengavaxia is licensed to be sold in 20 countries only. A total of three doses with a gap of 6 months after the first and second dose is the dosing schedule of Dengvaxia. WHO approves the vaccine for use in individuals of 9-45 years of age living in endemic areas and with a previous history of dengue infection confirmed by laboratory reports.

Dengvaxia is not approved or should not be given to individuals who:

• Have not been infected by any serotype of the dengue virus.
• Had any hypersensitive reaction to the previous dose of Dengvaxia
• Are suffering from severe immunodeficiency disease (HIV-positive patients).

Dengvaxia, when given to healthy people who have no history of Dengue, suffers from severe Dengue. Pregnant and lactating women are also contraindicated towards taking any dengue vaccine.

However, one should remember that Dengvaxia as a vaccine may not work in every individual living in the endemic area. Thus, it is recommended to continue using proper precaution methods to prevent dengue mosquitoes from biting and transmitting this dangerous disease.

The question still arises that how successful is Dengvaxia in those twenty countries where it is licensed. In April 2016, Dengvaxia was launched commercially in the Philippines. The country kicked off a mass immunization program to vaccinate a million students by the end of the year. More than six months into the immunization program, more than 830,000 children had received at least one dose of the vaccine. However, after reanalyzing its trial results, Sanofi confirmed that the people who had taken dengvaxia without a prior history of dengue infection are vulnerable to severe illness. As a result, Sanofi changed the vaccine label. The new drug label stated that the vaccine should only be given to people who have already been exposed to the dengue virus. Thus the immunization drive in the Philippines was immediately suspended. The vaccine came under deep controversy after the death of 10 children in the Philippines linked to Dengvaxia.

The European Commission in December 2018 granted regulatory approval to Sanofi for marketing. The marketing approval was based on providing clear indications that Dengvaxia should only be used in individuals of nine to 45 years who had a history of dengue infection confirmed by laboratory reports and must be living in dengue-endemic regions.

At present, clinical trials carried out with Dengvaxia in Asia and Latin America have prevented 93% of severe dengue cases and reduced hospitalization due to Dengue by 80%.

Other vaccine candidates for Dengue that are under Clinical Trials or Research

1. DENVax by Takeda ( also known as TAK003)
   TAK003 or Takeda’s tetravalent dengue vaccine is made from the original DENV-2-PDK-53 vaccine. The DENV-2-PDK-53 vaccine has been attenuated by adding mutations in Nonstructural protein 3(NS3). As per the phase 1 and phase 2 clinical trials reports, the vaccine is safe and tolerable. The phase 3 trials of the TAKOO3 vaccine have shown promising results. The vaccine prevented dengue-based hospitalization in 83.6% of the trial population and has reduced the illness in 62% of the trial population.
2. LAV Delta 30 or TetraVax-DV by the National Institute of Health (NIH)
   The NIH’s LAV Delta 30 or TetraVax-DV vaccine is being studied under two types of formulations, i.e., TV003 and TV005. This vaccine has a unique character in that it eliminates 30 contiguous nucleotides and thus weakens the four serotypes of the dengue virus. The human trial phase 1 and phase 2 results of TV003 have shown the vaccine’s success in safety and immunogenicity. The vaccine is under phase 3 trials.
3. TDENV-LAV and TDENV-PIV by the US Walter Reed Army Institute of Research (WRAIR), in collaboration with GlaxoSmithKline (GSK)
4. Plasmid DNA vaccine (TVDV) developed by the US Walter Reed Army Institute of Research (WRAIR), together with the US Naval Medical Research Center (NMRC)
5. V180, a recombinant protein-subunit dengue vaccine developed by Merck Sharp and Dohme

Dengue Vaccine in India

The Indian Council for Medical Research (ICMR) does not currently recommend the Dengvaxia vaccine for treating Dengue because of the following reasons:

• Absence of seroprevalence data in the 9-15 year population
• The minimum requirement of 3 doses
• Modest efficacy of dengvaxia (56-60%)

However, India is gearing up its scientific research and efforts towards developing a dengue vaccine and carry out preclinical and early phase human trials as early as possible. India has two potential dengue vaccine candidates in the pipeline. The first vaccine candidate is a live-attenuated dengue vaccine called TetraVax-DV. This vaccine has been developed by the National Institutes of Health (NIH), USA. Furthermore, the Indian vaccine producers Panacea Biotec, Serum Institute, and Biological E have obtained non-exclusive licenses for the TetraVax-DV vaccine’s clinical development and commercialization.

The second vaccine is a tetravalent (4-in-1), single-component, non-replicating, protein-subunit dengue vaccine termed “DSV4”. The pharmaceutical giant Sun Pharma in Mumbai and the International Centre for Genetic Engineering and Biotechnology (ICGEB) in New Delhi have indigenously developed this vaccine.
The researchers indicate that the “Made-in India” vaccines could be available in the next four to five years.

REFERENCES

1. Dengue Vaccine. Accessed at
   https://www.cdc.gov/dengue/prevention/dengue-vaccine.html
2. George S. L. (2014). Prospects for a dengue vaccine: progress and pitfalls. Missouri medicine, 111(4), 337–342.
3. Vaccines and immunization: Dengue. Accessed at
   https://www.who.int/news-room/q-a-detail/dengue-vaccines#:~:text=Vaccine%20efficacy%20against%20confirmed%20dengue,against%20severe%20dengue%20was%2079.1%25.
4. Dengvaxia, USFDA. Accessed at
   https://www.fda.gov/vaccines-blood-biologics/dengvaxia
5. Bharati, Kaushik & Jain, Hemant. (2019). Dengue vaccines: Current status and future prospects. Journal of Clinical and Diagnostic Research. 13. AB01-AB02.
   DOI: 10.7860/JCDR/2019/20714.12962
6. Torresi, J., Ebert, G., & Pellegrini, M. (2017). Vaccines licensed and in clinical trials for the prevention of Dengue. Human vaccines & immunotherapeutics, 13(5), 1059–1072. https://doi.org/10.1080/21645515.2016.1261770
7. The dengue vaccine dilemma. Accessed at
   https://www.pharmaceutical-technology.com/features/dangvaxia-philippines/
8. Massey, F. K., & Yulia, R. (2019). REVIEW ARTICLE: DEVELOPMENT AND USING DENGUE VACCINE FOR DENGUE INFECTION VIRUS. Medical and Health Science Journal, 3(2), https://doi.org/10.33086/mhsj.v3i2.1194
9. Swaminathan S, Khanna N. Dengue vaccine development: Global and Indian scenarios. Int J Infect Dis. 2019 Jul;84S:S80-S86. doi: 10.1016/j.ijid.2019.01.029. Epub 2019 Jan 23. PMID: 30684747.
10. Dengue vaccine for India? Not now. Accessed at
    http://www.cidsindia.org/dengue-vaccine-for-india-not-now.html