Sanofi-Pasteur released a media report on 29 November, warning that dengue-naive people would be at higher risk of a more severe infection if they were infected with dengue following vaccination with Dengvaxia – Sanofi Pasteur’s dengue vaccine that is also licensed for use in Singapore.

This warning was based on the analysis of 6 years of follow-up clinical data post-vaccination, the specific results of which are not in the public domain.

The silver lining was that the vaccine remained protective at 6 years if those vaccinated had been infected with dengue at least once prior to vaccination.

The company now recommends that the vaccine should not be offered to those who had previously not been infected with dengue. This was already a soft recommendation by our Health Sciences Authority (HSA) when it approved the vaccine for local use last year, but the current report by Sanofi Pasteur ups the stakes to ensure that testing for prior dengue infection is done before administering Dengvaxia.

This unusual effect – where the vaccine is less effective (and even harmful) in those with no prior dengue infection – is believed by a number of local and international experts to be caused by the paradoxical response by our immune systems to dengue and other flaviviruses (the antibody-dependent enhancement – or ADE – effect), although Sanofi Pasteur has downplayed this.

There are a number of articles that describe ADE in dengue well, including Wikipedia. Essentially, after the first dengue infection, the individual develops antibodies that render cross-protection against all 4 dengue serotypes for a short period. This protection is relatively short-lived and wanes after a few months to years. When infected by a second, different, dengue serotype years later, the individual’s immune system triggers a rapid heightened response against the original dengue serotype and a much weaker response against other dengue serotype. The antibodies produced do not neutralize the virus, but instead, may act as “Trojan horses” that facilitate virus infection of monocytes (their target cells), and result in a more severe infection. The following image from Nature’s Scitable shows the cellular events clearly.

The educational article on host response to dengue is well worth a read for those who are interested. In the context of Dengvaxia and ADE, it is postulated that the vaccine acts as that first infection for those who has previously not been exposed to dengue. For those who stock and prescribe the vaccine in Singapore, this new update by Sanofi Pasteur provides compelling reasons to be certain that Dengvaxia should only be administered to those with serological or strong clinical evidence of prior dengue infection, thus limiting its market significantly.