The Philippine Medical Association (PMA) has urged President Marcos to intervene and expedite the approval of new-generation dengue vaccines amid the surge of dengue cases in the country.
The appeal was made by the country’s doctors at the launching of the Empowering Networks to Defeat Dengue or End Dengue Coalition—founded by PMA, in partnership with health-care organizations, the academe, researchers and advocates—on Tuesday in Quezon City, with the collective goal of achieving zero dengue deaths by 2030.
In a letter addressed to Mr. Marcos read during the event by Dr. Erica Tania Davillo, chair of the PMA’s ad hoc committee on dengue advocacy, the organization acknowledged that the safety of dengue vaccines was of “utmost concern” because of the country’s previous experience with Dengvaxia.
The PMA specifically cited Qdenga of Japanese pharmaceutical company Takeda, which is approved in 40 countries and one of the only two dengue vaccines approved by the World Health Organization (WHO) to prevent dengue in highly endemic countries like the Philippines. (The other WHO-approved dengue vaccine is Dengvaxia of French pharmaceutical giant Sanofi Pasteur.)
The WHO in May last year cleared Qdenga for use in children aged 6 to 16 in areas with high infection rates. The prequalification made it eligible for procurement through United Nations agencies like the UN Children’s Fund. The vaccine, which contains weakened versions of the four dengue virus strains, is recommended as a two-dose schedule with a minimum interval of three months between doses.
Dengue disease is caused by infection with dengue virus, which is transmitted to humans through the bite of mosquitos. This vaccine contains attenuated versions of the 4 virus serotypes. These versions cannot cause the disease, but they ‘teach’ the immune system (the body’s natural defences) to defend the body against the virus. When a person is given the vaccine, the immune system identifies the attenuated serotypes as foreign and makes antibodies against them. When a person is later exposed to the virus, the immune system recognises it and can quickly make many more antibodies, which then neutralise the virus before it can cause dengue disease.
so it's not an mRNA vaccine but an old fashioned attenuated virus type.
But the complications of dengue happen in folks who have had the disease before, and get a hyperimmune response. That was the problem with Denguevax.
lancet article.
Cumulative vaccine efficacy against virologically confirmed dengue was 64·2% in dengue-exposed participants and 53·5% in dengue-naive participants from first dose up to 4·5 years after the second dose.
lancet article link
article on NATURE from 2023
Is new dengue vaccine efficacy data a relief or cause for concern?
The exact immunopathogenic mechanisms of sequential heterotypic DENV infections are incompletely understood, but considerable evidence points to humoral and cellular adaptive immune responses occurring in response to the first infection facilitating increased DENV replication during the second infection which, in turn, drives pro-inflammatory cytokine secretion25,26,27,28,29,30,31. The exact number of annual dengue fatalities is not known but the estimates range between 5000 and 40,000 with many deaths occurring in children32,33.
with dengevax, the immune problem includes:>
Dengvaxia® Sanofi Pasteur licensed the first dengue vaccine (Dengvaxia®) in Mexico in 2015, and more than 20 countries thereafter, based on the safety and efficacy demonstrated in two phase III trials and a single season of disease surveillance. Unfortunately, the optimisim that a dengue vaccine was finally available quickly became disappointment when a safety signal was observed in vaccine recipients who were dengue non-immune at the time of vaccine administration44,45. In the third year of the phase III clinical trial, the youngest, non-immune vaccine recipients experienced increased rates of hospitalized and severe dengue compared to their unvaccinated peers
The next generation of dengue vaccines As expected, every dengue vaccine candidate following Dengvaxia® is being stringently reviewed for safety and efficacy in dengue immunes and non-immunes, across a broad age range of recipients, and for their ability to protect against the full spectrum of disease outcomes caused by infection with any DENV type. There is also a requirement for demonstrating safety and efficacy across more than one dengue season56,57,58.
Two new live attenuated dengue vaccines have now completed phase III efficacy trials and there is room for cautious optimism once again. Takeda recently received approval from Indonesia, European Commission, and Brazilian regulators for use of their two-dose vaccine (TAK-003) in people 4 years of age and older, regardless of baseline dengue immune status.
(https://www.takeda.com/siteassets/system/newsroom/2022/qdenga/ema-combined-h-5155-en.pdf) (accessed 21 January 2023).
https://butantan.gov.br/noticias/butantan%27s-dengue-vaccine-has-79.6-efficacy-partial-results-from-2-year-follow-up-show
In summary, the three live attenuated dengue vaccines which have generated clinical endpoint efficacy data have all demonstrated; (1) higher efficacy in dengue immune recipients; (2) higher efficacy against more severe clinical phenotypes; (3) variance in DENV type specific efficacy, and (4) the challenge of capturing data for all desired clinical endpoints (any dengue, severe dengue, hospitalized dengue), across all DENV-1–4 types, in both dengue immune and non-immune recipients.
one of the problem with attenuated virus vaccines is that sometimes the virus escapes and causes the disease (a major problem with the Oral Polio vaccine).
How to assess for the potential of vaccine-associated dengue is not straight forward. After two years of surveillance in the Butantan study there were no severe dengue cases nor cases with clinical warning signs. The Takeda experience, however, is more complex, and even though clinical and regulatory review committees for the European Commission and Brazil’s National Health Surveillance Agency (ANVISA) did not believe there was a safety signal in dengue non-immune recipients, this a point of contention
Conclusion It is clear the perfect dengue vaccine is not on the immediate horizon, but the Sanofi, Takeda, and Butantan/NIH/Merck experiences do inform us that it is possible to effectively immunize some people against disease scenarios that constitute dengue’s burden. I would contend when it comes to dengue countermeasure development, safety is non-negotiable, but all other expectations must be managed and considered in the aggregate. Our challenges with effectively communicating coronavirus disease 2019 vaccine performance characteristics should be a cautionary tale in this regard. Pursuit of the perfect dengue vaccine is a laudable goal, but not at the cost of overlooking imperfect options that could safely deliver tangible, albeit smaller scale, public health benefit.
I post the text and links etc so I can read these articles in detail on my tablet. QDenga page
hmmm...it says a lot about the politics of this vaccine that it has a long list of places for you to share the article, but X/twitter is not one of them.
No comments:
Post a Comment