ANTI­-DENGUE VACCINE BRINGS HOPE

ANTI­-DENGUE VACCINE BRINGS HOPE

Drishya rajan,4th  Pharm.D

Denque a mosquito bone flaviviral infection caused by antigenically distinctive 4 serotypes (DEN 1-4) Of virus. Particularly in the tropical and sub tropical area in the world, with almost 40% world population residing there. WHO estimate that 50-100 million dengue infection occurs annually.

Dengue clinical significance range from asymptomatic infection to classical and severe dengue fever like Dengue haemorrhagic fever(DHF) and Dengue shock syndrome(DSS) and complication with sequential infection with DENV(Dengue virus) also there, But there is no specific anti-viral therapy and treatment only supportive.

Mexico has granted sanofi pasture marketing authorization for its tetravalent dengue vaccine, marketing first in the world,to be licenced for the prevention of dengue. The US FDA has granted fast tract designation recognizes that a dengue vaccine would address an important medical need for a serious disease. The federal commission for the protection against sanitary risk (COFEPRIS) has approved the tetravalent dengue vaccine for the prevention of disease caused by 4 dengue virus serotype in preadolescent and adult. Having age between  9-45 years,living or travelling in endemic countries, including expertise and military personals.

SANOFI PASTURE’S DENGUE VACCINE CLINICAL PROGRAMME

Sanofi pastuer’s investigational dengue vaccine- Target all 4 virus type which has been evaluated in phase1 and phase2 clinical trials in children and adult in US, Africa and Asia. The immune response against all 4 serotypes was observed after 3 doses of the vaccine. The vaccine is well tolerated with a similar safety profile after each dose. The large scale phase 3 trials studies in 31,000 adult and children conducted in latin America, which follows higher standard from international conference on harmonisation of technical requirement for registration of pharmaceutical for human use (ICH).

LIVE ATTENUATED TETRAVALENT DENQUE VACCINE

Live attenuated vaccine virus are capable of producing robust immune response, immune memory closely similar to that induced in natural infection. Live attenuated vaccine having tetravalent formulation producing a balance neutralising immune protective response  against all 4 serotypes. Vaccine will be safe and non reactogenic and show restricted replication in human , however such clinical infection characterized by mild rash, transient leukopenia and mild elevation of liver enzyme are included as accepted ADR.

An accepted level of vireamia range from 10^.5-10^2.5 plaque forming unit (pfu/ml). The vaccine candidates namely DENV-145AZ5 PDK 20, DENV-2S16803 PDK 50, DENV-3CH53489 PDK 20 and DENV-4341750 PDK 20

SAFETY AND EFFICACY

Primary efficacy trials was conducted based on the number of virologically confirmed dengue (vcd) case of any virus serotype in vaccinated and control subjects. Vaccine efficacy against any one of the 4 serotypes was 59.2%. In the pooled analysis(intention to treat analysis) from dose 1 the vaccine efficacy was higher against  serotype 3 and 4(71.6% and 76.9% respectively) than against serotype 1 and 2 (54% and 43% respectively). In the interim analysis(for long term safety analysis )shows there is a cumulative benefit against hospitalized and severe dengue case . while the efficacy was reported up to 1-2 year after the vaccination.Although cases of hospitalization and severe dengue case those receives vaccine was seen in 3 year, which is relatively small no of cases. Immunizers of 9 years of age or older, the relative risk for hospitalization in 3^rd year was 0.50 and was 1.58 less than 9 year of age.

Vaccine safety and efficacy estimated in the post dose 2, were consistent and encouraging in both phase3 trials. Variety of outcomes measures including,the vaccine efficacy varied by serotype, age at vaccination and serostatus prior to administration.

PROSPECT OF DENGUE VACCINE IN INDIA

In the past decades, India shows increased trend in the number of reported dengue case, Which steady increase from 5534 in 2007 to 75,454 in 2013 according to national vector bone disease control programme (NVBDCP).With  improvement insurvillence system and efficient management of cases, the case fatality rate due to severe dengue has declined from 3.3% in 1996 to 0.4% in 2010.Due to repeated out break and endemics there has been significant increase in the financial burden to the health care sector. This emphasises the need for a cost effective dengue vaccine as preventive strategy.