Taiwan - Dengue vaccine: T-cell responses and vaccine protective efficacy

Issues and Objectives

Dengue virus belongs to the genus Flavivirus in the family Flaviviridae. Based on different serotypes, it is divided into four types: I, II, III, and IV. Each serotype is capable of causing infection and disease. If a patient is infected with one type of dengue virus, they will only have lifelong immunity to that type. However, they will only have short-lived immunity to other types of dengue virus, lasting only 2 to 9 months. If they are subsequently infected with a different type of dengue virus, there is a potentially fatal risk, including dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Antibody-dependent enhancement (ADE), or the antigenic sin effect produced by the antibody-T cell reaction, is considered to be a possible cause of severe dengue fever.

※Antibody-dependent enhancement (ADE): This refers to a situation where, after a host is infected with a certain type of dengue virus, although the body has neutralizing antibodies against that type, the ability to neutralize other serotypes of the virus is insufficient. Consequently, when infected with a different serotype of dengue virus in the next infection, the virus infection is enhanced.

※Antigen stigma effect: The T cell response caused by the first dengue virus infection may lead to incomplete activation of T cells when infected with a different type of virus a second time, due to the difference in antigens between the two, resulting in reduced protection and thus severe illness.

Therefore, an ideal dengue vaccine should achieve a balanced immune response against all four serotypes of the virus in order to combat all serotypes of dengue virus.

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Improvement Measures Taken

Research on dengue fever vaccines began in the 1940s, with Sabin and Schlesinger et al. first developing a monovalent attenuated Hawaiian dengue vaccine using mouse brains. Starting in the 1970s, the virus was domesticated through tissue culture. With advancements in scientific research technology, the use of recombinant DNA techniques for viral gene replacement in recent years has led to groundbreaking progress in dengue vaccine research.

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Results

The following are some vaccines that are currently under development:

1. Live attenuated vaccines: The virus undergoes a series of culturing processes to reduce its pathogenicity, but it can still elicit a sufficient protective immune response for use as a vaccine. The disadvantage is that the viral strain may lose its ability to elicit an immune response due to over-attenuation, or insufficient attenuation may cause pathological reactions in the recipient.
2. Chimeric live attenuated vaccine: This is currently the most advanced product, a quadrivalent dengue vaccine (CYD-TDV) developed by Sanofi. It uses the already approved yellow fever virus 17D (YFV-17D) vaccine as its backbone, and carries the structural proteins (precursor membrane protein and mantle protein, prM/E) of four dengue virus serotypes. It has completed phase III clinical trials. A drawback is its poor protective efficacy against serotype 2.
3. Deactivated vaccines are relatively safe and more likely to elicit an average immune response. However, they lack immunogenicity against non-structural proteins and require adjuvants to enhance the immune response.
4. Subunit vaccines: The dengue virus's envelope proteins (E) are most commonly used as immunogens. The most advanced vaccine currently is the DENV-1 monovalent DNA dengue vaccine, developed by the U.S. Navy Medical Research Center. It is currently in Phase I trials, but the neutralizing antibody response has been unsatisfactory. The trial has now been restarted in collaboration with Vical, using the company's adjuvant (Vaxfectin®) specifically designed for DNA antigens.
5. T-cell immune response: This mainly utilizes the immune response of CD4+ T cells. However, current research results indicate that the impact of the T-cell response induced by the quadrivalent dengue vaccine on the vaccine's protective efficacy requires more careful evaluation.

Due to climate change, the future climate will be more favorable for the survival of disease-carrying mosquitoes, which may increase the scale and severity of dengue fever outbreaks in Taiwan. This case review of the vaccine development process can serve as a reference for future vaccine development. This epidemic prevention information can be regarded as an adaptation strategy to strengthen the public health epidemic prevention system in response to future climate change.

Glossary

Climate change risk assessment: Using effective assessment tools to understand the medium- and long-term impacts of climate change on various sectors, and to propose corresponding adaptation strategies and actions to reduce the risks brought about by climate change.

Case type:

Structural and physical options: engineering techniques or reinforcement of existing structures, integrated technology development

Social options: learning and exchanging disaster knowledge in the community, and developing and applying early warning information.

Institutional options: Establishing institutions at the economic, policy, and legal levels

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References

Recent Developments in Dengue Fever Vaccines: Research on the Protective Effect of T-cell Responses on Vaccine Efficacy, Xiao Yuru and Pan Jianxiong, Journal of Infection Control, Vol. 26, No. 5, pp. 210-217.

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Reference Websites

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