ANTI–DENGUE VACCINE SOON!

            ANTI–DENGUE VACCINE SOON!

PROF WAQAR HUSSAIN

                    Dengue fever is caused by four closely related serotypes DV1, DV2, DV3, D4 viruses of genus flavivirus carried by mosquito Aedes aegypti most abundant in tropical and sub-tropical regions. Dengue infection can result in a range of clinical manifestation from asymptomatic infection (80%) to dengue fever (10-15%) and the severe disease (5% -10%) of dengue hemorrhagic fever or dengue shock syndrome, which are fatal if not managed properly. Infection to one serotype produces life-long immunity, by the production of antibodies, against infection by the same serotype but only short term and partial protection against infection with other serotypes.

                The presence of antibodies of one serotype pave the way for dengue hemorrhagic fever through immune enhancement as virus/non-neutralizing antibody complexes preferentially engulfed cells of immune system ,enabling the virus  multiplication unchecked and thus the teeming population of virus results in severe infection often lethal. So, development of vaccine which produces “immune response” against all four serotypes is absolutely necessary as about 3 billion people of more than 110 countries (every second person) are at risk, 230 million gets  dengue infection annually, 2 million (less than 1% of dengue patients)- mostly children – develops severe form of dengue hemorrhagic fever. About 2 million gets hospitalization and 25000 dies. Mortality is about 5% without treatment and 1% with adequate treatment.

               Dengue has increased 30 fold in last 50 years. Most countries are relaying on aged long mosquito control methods. They are not learning lesson from history; mosquito is more than 150000000 years old specie and had sustained in the extreme severity of conditions of all ages that mankind even not dare to think. Then how it will succumb to these mild measures of mankind, so an inside remedy is to be provoked to combat the onslaught of this tiny fierce creature at molecular level, anti dengue vaccine and anti viral drug is the viable solution. Vaccination saves about 2.5 million people every year but more than 2 million people still die due to lack of access to vaccine.

             Look at Sri Lanka where mortality rate had diminished to half this year due high level training, awareness campaign, introduction of new testing devices and strict observance of precautionary measures. On the other hand, dengue cases have increased than previous years with 11, 250 until April along with 55 deaths. In spite of cleaning operation, garbage disposal, persistent fogging, spraying Bti (bacillus thuringiensis israelenis-are bacteria which infects and kills mosquito larva) and strict surveillance of mosquito colonized areas and stern execution of dengue control laws as 2191 dengue linked arrests and about four million rupees fine were collected until April from mosquito breeders.

                  The shrewd mosquitoes have found new places to breed in cemented walls instead of usual breading places of home garden, water channels, etc. So, development of vaccine is indispensable to check the spread of disease, said Dr. Paba Pallihawardene, head of entomological department.

                     She disclosed, “We will have anti dengue vaccine by 2015, trials are underway, as all other methods of controlling the spread of dengue have proved not effective.”

                     The preparation of vaccine to counter all serotypes has one major threat that vaccine will enhance the risk of severe disease through antibody-dependent enhancement (ADE). So an ideal vaccine should be safe, efficacious, wraps all variants of viruses, doesn’t contribute to ADE, transportable, easily storable and inexpensive.

                      Apart from Sri Lanka, Chinese are focusing to produce tetravalent vaccine by integrating four monovalent components and developed a genetic vaccine based on novel adeno-associated viral (AAV) vector expressing the carboxyl-terminal, truncated envelope protein of dengue virus. AAV was injected into mice and antigen of dengue virus was produced that induced production of antibody and thus long lasing immunity developed against dengue virus.

                 Philippine is also struggling to produce anti dengue vaccine in the laboratories of the Department of Health (DOH) in Cebu and Laguna by joint efforts of Filipino and foreign experts. Dr Janario, Director DOH said: “Philippine was chosen because it is the one of the nation affected by dengue. We have experts, the facility, the data and the surveillance system. There are four strains of dengue and you can find them all here.”

                In Cuba, vaccine is currently being tested on monkey and will advance to clinical trial on human if the results are satisfactory, said Dr. Gerardo Guillen, Research Director of International Centre for Genetic Engineering and Biotechnology (Cigb). Dr. Guillen disclosed vaccine has effectively controlled the multiplication of virus in monkeys. Vaccine is designed to act on all the four variants of the dengue virus. Cigb is working with France’s Pasteur institute to develop the vaccine.

             At present, many international pharmaceutical companies are developing vaccines by using the virus itself. It is an old method to use infectious but attenuated virus to produce strong long lasting immunity.

             Sanofi Pasteur of Lyon, France has developed a live attenuated virus vaccine that produces antibodies against all four serotypes in preliminary studies, but for some reason, one strain of virus (DEN-2) was still able to infect children who received the vaccine. Now a much larger trial involving 31,000 adults and children of 10 different countries of Asia and Latin America is under way. Full details of study are expected in scientific paper this month.

            Sanofi is five years ahead of other vaccine producing ventures. Reuter revealed that 4000 Thai children have received vaccine and if their body developed sufficient immunity countering all four strains, Sanofi will submit his therapy for medical vetting in the USA in November 2012. Sanofi has invested $ 440 million to build a pharmaceutical factory in France, one of the largest pharmaceutical companies of the world, to manufacture vaccine. Health experts are optimistic that the vaccine could now go to market in 2014 or even earlier.

              Health experts fear that heavy commercial investment could mean that Sanofi’s vaccine will be costly, which is a letdown as dengue normally afflicts those who cannot afford. Health experts also believe that company will achieve both medical and commercial successes as 3 billion at risk people are waiting for vaccine.

             Sanofi product will be delivered in three separate shorts, in a span of 12 months in order to effectively fight the dengue virus. Health experts lamented this long period for patient to combat the disease and more window of opportunity for the virus to sow terror. However Duane Gubler USA expert awith 40 years experience of tracking dengue movement said, “Everything they have done so far looks very good.” His compliment made Sanofi cheerful with hope of getting one billion euro annually once the dengue cure has been rolled out successfully. Sanofi disclosed that vaccine has yet to be given commercial name.

                   The journey of developing vaccine has been started in 1940’s but now we are seeing the blurred view of our coveted destination. One can infer and hope from the above developments that anti dengue vaccine will be available in market soon. In a nutshell, we can say: “Drug to detonate; deadly, dangerous, dreadful, damnable dengue is developing…. and will be divulged then dispersed for distribution, for the disappointed, disheveled diseased”.