Preparing for dengue vaccine introduction

Large scale phase 3 clinical evaluation of a tetravalent live recombinant dengue vaccine (CYD-TDV, Sanofi-Pasteur) in >30 000 individuals from Asian and Latin American countries confirm its protective efficacy.^{3, 4} Safety data from the clinical studies indicate that local and systemic adverse reactions are comparable to those recorded for other available live attenuated vaccines. No safety concerns have been identified. The safety profile of CYD-TDV reported from the 2 phase 3 studies is consistent with the phase 2b data previously published and reviewed by GACVS.⁵

Preparing for the launch of this vaccine, guidance on safety monitoring will be required. In a preliminary review of risks that should be considered the Committee noted at least 4 groups of issues: (i) the theoretical possibility of more severe dengue cases over time post-immunization due to prior stimulation of the immune system; (ii) events related to the vaccine component, in particular the genetically modified yellow fever vaccine virus; (iii) risks in populations with specific conditions (immune deficient persons, pregnant or lactating women, patients with chronic diseases); and (iv) risks related to co-administration with other vaccines as part of a national immunization programme.

Monitoring these risks will require a well-defined strategy. GACVS confirmed the broad approaches proposed earlier that include dengue fever surveillance, vaccine introduction designs that would allow for hypothesis testing, and active surveillance for selected adverse events following vaccination that could be rare but potentially severe. The Committee concluded that advice on risk management should be developed, in parallel with that of the manufacturer, in order to assist early introducing countries to assess the safety of this important new public health tool. This would include long-term collection of population based data, particularly to assess immune enhanced dengue-related events resulting from vaccination or natural infection. After introduction of CYD-TDV, the safety of the vaccine will need to be monitored closely together with its effectiveness. Due to the need to monitor possibly rare events with reliable diagnosis, it would be desirable to conduct multicentre studies.

³Capeding et al. Clinical efficacy and safety of a novel tetravalent dengue vaccine in healthy children in Asia: a phase 3, randomised, observer-masked, placebo-controlled trial. Lancet 2014; 384:1358-65.

⁴Villar et al. Efficacy of a tetravalent dengue vaccine in children in Latin America. NEJM e-pub 3 November 2014.

⁵See No. 6, 2013, pp. 68–69.

Full report of GACVS meeting of 3-4 December 2014, published in the WHO Weekly Epidemiological Report on 23 January 2015