A Forum parallel session on 9 November afternoon heard about exciting progress in vaccine development against bacterial pathogens and malaria.
Catch up campaigns with a fractional dose of PCV
In settings with low routine coverage of pneumococcal conjugate vaccines (PCVs), mass campaigns might help to establish herd immunity but would be costly. A possible alternative would be ‘fractional dosing’ – using a fraction of the recommended dose.
Dr Issaka Soumana, Epicentre, Maradi, Niger, in collaboration with Dr Rebecca Grais (Epicentre, Paris, France) and colleagues in Kenya and Niger, presented the results of a trial of fractional dosing in Niger. A total of 63 villages were involved in the trial, with children aged 1–9 years in each village being given either a standard dose of PCV10, one-fifth of the standard dose or no vaccine.
Both the standard dose and the fractional dose led to a significant drop in pneumococcal carriage at a 6-month follow-up point. An initial analysis suggests that fractional dosing is non-inferior to the full dose with a 7.5% non-inferiority margin. However, the PCV coverage rate was higher than anticipated as baseline, and further data analysis will be required to determine whether fractional dosing is an appropriate strategy for a PCV campaign.
Blocking malaria transmission
With two malaria vaccines now approved, these are notable days for malaria vaccine development. A remaining challenge is a transmission-blocking vaccine, which would prevent malaria parasites from being transmitted from one patient to another. Mr Jordan Plieskatt, from Michael Theisen’s group in Denmark, described promising progress made with colleagues from Burkina Faso and Mali on a transmission-blocking and multi-stage vaccine targeting Pfs230 and Pfs48/45 proteins.
A production process has been established to generate material for trials – R0.6C, a first-generation transmission-blocking vaccine, and ProC6C, a novel fusion protein designed to be a multi-stage malaria vaccine. A phase I first-in-human trial in Burkina Faso has shown that both are safe and well-tolerated. Immunogenicity was enhanced by the use of Matrix-M adjuvant.
In addition, ProC6C was shown to elicit functional antibodies with transmission-blocking activity in mosquito membrane feeding assays. ProC6C is now due to evaluated in a phase II trial due to start in Mali before the end of 2023 and in a human challenge model.
TB prevention in newborns
Although BCG is in widespread use to prevent TB in newborns, it has several drawbacks. Dr Ingrid Murillo Jelsbak, Biofabri, Spain, presented the latest data from a phase IIa trial, carried out with colleagues in South Africa, of a possible alternative vaccine, MTBVAC.
Nearly 100 newborns in South Africa were vaccinated with either BCG or one of three doses of MTBVAC. MTBVAC was safe and well tolerated, and highly immunogenic at all doses tested. The results were used to select an appropriate dose of MTBVAC for a phase III trial in a high-burden setting, launched in 2023 in South Africa, which aims to recruit more than 7000 participants.
Oral polio vaccine – benefits beyond polio?
As well as protecting against target infections, there is evidence that some vaccines, including oral polio vaccine, have more general beneficial effects, reducing under-3 mortality by up to 35% in some studies. Dr Sebastian Nielsen, University of Southern Denmark, Odense, Denmark, has worked with Professor Peter Aaby (Bandim Health Project, Bissau, Guinea-Bissau) and colleagues in Bangladesh, Ghana and Kenya to explore these ‘non-specific effects’ (NSEs) further.
Dr Nielsen analysed routinely collected Health and Demographic Surveillance System data to explore the mortality of young children before and after campaigns with oral polio vaccine in different countries. Although only a minor effect was seen in rural Ghana, all-cause mortality fell by 35% in urban Bissau and 31% in Chakaria, Bangladesh, while mortality and hospitalisations fell by 36% in Burkina Faso. Based on the Guinea-Bissau results, OPV averted 10% (5-15%) of all childhood deaths during the analysis period.
Oral polio vaccine is currently being phased out – something that, Sebastian suggested, might have unanticipated negative effects on child health.
Dr Gabriella Scarlatti, IRCCS Ospedale San Raffaele (Italy): PedMAb1 clinical trial: Safety assessment of CAP256V2LS to prevent breastmilk HIV transmission in HIV-1 exposed uninfected neonates
Dr Nouhoun Barry, University of Tübingen (Germany): Assessment of naturally acquired humoral immunity against malaria protecting against controlled human malaria infection (CHMI)