Malaria parasites in mosquito midgut
Malaria parasites in mosquito midgut

A followup study 1 of the most successful malaria vaccine to date is not very impressive:

In cohort 2, adjusted efficacy of the RTS,S/AS02A candidate malaria vaccine against first or only clinical malaria episodes in Mozambican children aged 1 to 4 years was of 35.4% during the first six months of follow up (ATP cohort), decreasing to 9.0% in the subsequent 12 months. 1

(My emphasis)  In  the earlier clinical trial, this vaccine had been moderately effective, 2 something like 35-65% efficacy — pretty feeble, but better than other malaria vaccines.  And in one subset of children, the protection seemed to last reasonably well, remaining roughly constant for 21 months. 3   But in this second group of vaccinated children, the protection dropped like a rock.  Why?

The most likely difference is that children in the second (poor long-term protection) group were treated for malaria.  That means the first group was constantly re-exposed to malaria parasites, which acted as a vaccine booster.  The second group didn’t get that booster effect, and their immunity dropped.  (The first group was also in a higher-risk area, again meaning they were more likely to be re-exposed to the parasite.)

Children in cohort 1 were probably exposed to low-density parasitaemias for a longer time than children in cohort 2, in which the development of this enhanced asexual-stage immune response may have been impaired. We propose this may explain a waning of the vaccine-specific protective response in cohort 2. 1

Does this mean the vaccine is useless?  Not at all.  In high-risk areas this can clearly reduce disease.  But equally clearly, this isn’t likely to be helpful for eradicating malaria, because the more successful this vaccine is at reducing malaria, the less effective it will become.

  1. Guinovart, C., Aponte, J., Sacarlal, J., Aide, P., Leach, A., Bassat, Q., Macete, E., Dobaño, C., Lievens, M., Loucq, C., Ballou, W., Cohen, J., & Alonso, P. (2009). Insights into Long-Lasting Protection Induced by RTS,S/AS02A Malaria Vaccine: Further Results from a Phase IIb Trial in Mozambican Children PLoS ONE, 4 (4) DOI: 10.1371/journal.pone.0005165[][][]
  2. Abdulla, S., Oberholzer, R., Juma, O., Kubhoja, S., Machera, F., Membi, C., Omari, S., Urassa, A., Mshinda, H., Jumanne, A., Salim, N., Shomari, M., Aebi, T., Schellenberg, D. M., Carter, T., Villafana, T., Demoitie, M. A., Dubois, M. C., Leach, A., Lievens, M., Vekemans, J., Cohen, J., Ballou, W. R., and Tanner, M. (2008). Safety and immunogenicity of RTS,S/AS02D malaria vaccine in infants. N. Engl. J. Med. 359, 2533-2544. doi:10.1056/NEJMoa0807773

    Bejon, P., Lusingu, J., Olotu, A., Leach, A., Lievens, M., Vekemans, J., Mshamu, S., Lang, T., Gould, J., Dubois, M. C., Demoitie, M. A., Stallaert, J. F., Vansadia, P., Carter, T., Njuguna, P., Awuondo, K. O., Malabeja, A., Abdul, O., Gesase, S., Mturi, N., Drakeley, C. J., Savarese, B., Villafana, T., Ballou, W. R., Cohen, J., Riley, E. M., Lemnge, M. M., Marsh, K., and von Seidlein, L. (2008). Efficacy of RTS,S/AS01E vaccine against malaria in children 5 to 17 months of age. N. Engl. J. Med. 359, 2521-2532. doi:10.1056/NEJMoa0807381[]

  3. Alonso PL, Sacarlal J, Aponte JJ, Leach A, Macete E, et al. (2005) Duration of protection with RTS,S/AS02A malaria vaccine in prevention of Plasmodium falciparum disease in Mozambican children: single-blind extended follow-up of a randomised controlled trial. Lancet 366: 2012–2018[]