Publication of results of 9-valent pneumococcal conjugate vaccine
trial in South Africa
A recently published paper presented the results of a 9-valent
conjugate pneumococcal (Pnc) vaccine trial undertaken in Soweto, South Africa
(1). Although the 7-valent Pnc vaccine proved to be highly efficacious in
the US (2,3), it was unclear how the vaccine would function in a developing
country setting, where there is likely to be a high disease burden. This is
due to geographical variations factors such as the Pnc serotype distribution
(6) and important co-factors such as HIV. This study was conducted in a low-income
setting with a high prevalence of HIV infection and Pnc antibiotic resistance
and specifically explored protection against related endpoints.
In the trial, three doses of a 9-valent Pnc vaccine (containing serotypes
1,4,5,6B, 9V, 14,18C, 19F and 23F) were administered to participants at
6, 10 and 14 weeks of age. The study demonstrated a protective effect against
first episode of vaccine serotype related invasive pneumococcal disease
(IPD) in both HIV negative (83% V.E. 95% c.i. 39-97%) and positive recipients
(65% V.E.; 95% c.i. 24-86%). Similar results in immuno-competent infants
for the 7-valent Pnc conjugate vaccine have been observed both in the American
Indian trial (2) (86% VE) and in Northern California (3) (94% VE). In the
South African trial, the efficacy was 50% if all IPD related vaccine serotypes
were considered. As previously observed (5), there was a lower but significant
vaccine efficacy against first episode of x-ray confirmed pneumonia (17%
V.E.; 95% c.i. 4-28). Furthermore, the incidence of IPD due to penicillin
resistant pneumococci was reduced by 67% VE (95% c.i. 19-88).
This study is thus congruent with previous conjugate vaccine trials for
IPD (2-5), partly on which basis the United States introduced a 7-valent
Pnc conjugate vaccine into its routine infant national immunisation programme
in 2000. Post-introduction disease surveillance in the US has since demonstrated
a large decline in invasive Pnc disease rates in both young children and
also adults, including the elderly (representing either a herd immunity
effect or direct impact of the polysaccharide vaccine) (4). The role of
serotype replacement (the emergence of disease causing non-vaccine serotypes)
remains unclear.
In the accompanying commentary, the potential role (and barriers, particularly
vaccine cost) for Pnc conjugate vaccine is discussed with a focus on low-income
countries, where the burden of pneumococcal disease is likely to be high
and where there is often also a high prevalence of HIV. Particularly, in
view of the high vaccine cost, it is also important to understand how many
doses are actually required to provide direct (and indirect) protection.
Globally in most countries, including Europe, Pnc national vaccination policy
is still evolving. To aid decision makers, it is critical to ascertain the
disease burden, the potential impact and cost of alternative interventions
in different settings – which includes understanding the contribution of
herd immunity and serotype replacement.