Stanton TD
Keegan SP
Abdulahi JA
Amulele AV
Bates M
Heinz E
Hooda Y
Hu W
Jain K
Kanwar S
Magobo R
Olwagen CP
Tembo JM
Sonda T
Strysko J
Tigoi CC
Amin SA
Bittinger K
Cornick J
Foster-Nyarko E
Gumbi W
Hotwani A
Iqbal N
Jones SM
Kabir F
Khan W
Musyani CL
McGann CM
Mittal V
Moustafa AM
Musicha P
Mwansa JCL
Ndumba ML
Odih EE
Omuoyo DO
Pearse O
Phillips LT
Planet PJ
Rasool AA
Rodrigues CMC
Sands K
Tanmoy AM
Theiller E
Zuza AM
Basu S
Chan GJ
Iregbu KC
Mazarati JB
Alemayehu SS
Walsh TR
Zahra R
Dramowski A
Fwoloshi S
Labi AK
Madrid L
Obeng-Nkrumah N
Ojok D
Wadugu BD
Whitelaw AC
Bethou A
Bhargava A
Jindal A
Nanavati RN
Prasad PS
Sastry A
Farooqi JQ
Ghanchi N
Jehan F
Khan E
Agarwal RK
Aiken AM
Berkley JA
Coffin SE
Feasey NA
Govender NP
Hamer DH
Madhi SA
Nisar MI
Saha SK
Saha S
Sankar MJ
Wyres KL
Holt KE
PLoS Med. 2026;23e1004879
BACKGROUND: Klebsiella pneumoniae causes ~20% of sepsis in neonates, with ~40% crude mortality. A vaccine administered to pregnant women, protecting against >/=70% of K. pneumoniae infections, could avert ~400,000 cases and ~80,000 deaths annually, mostly in Africa and South Asia. Vaccine formulations targeting the capsular polysaccharide (K) or lipopolysaccharide (O) antigens are in development. Global K. pneumoniae populations display extensive K and O diversity, necessitating a polyvalent vaccine targeted to the serotypes associated with neonatal disease in relevant geographical regions. We investigated the prevalence of K and O types associated with neonatal sepsis in Africa and South Asia to inform maternal vaccine design. METHODS AND FINDINGS: We analysed 1,930 K. pneumoniae neonate blood isolates from 13 surveillance studies across 35 sites in 13 countries. We used pathogen whole-genome sequencing to predict K and O serotypes and adjust for local transmission clusters, and Bayesian hierarchical meta-analysis to estimate K and O prevalence overall and per region, treating site as a random effect. Eighty-seven K loci were identified. KL2, KL102, KL25, KL15, and KL62 accounted for 49% of isolates. We estimate that 20 K loci, combining the eight most prevalent per region, could cover 72.9% of all infections (95% credible interval: [69.4%, 76.5%]) and >/=70% in each of Eastern, Western, and Southern Africa and South Asia. Preliminary findings from three sites suggested sufficient temporal stability of K loci to maintain 20-valent K vaccine coverage over 5-10 years, but more longitudinal data are needed to support this prediction. O types were far less diverse (n = 14 types). We estimate the top-5 (O1Ôì║beta,2Ôì║, O1Ôì║beta,2beta, O2Ôì║, O2beta, and O4) would cover 86.2% [82.6, 89.9%] of total infections (76%-92% per region), while the top-10 would cover ~99% of infections in all four regions. The main limitations of our study are the reliance on genome sequences to predict K and O serotypes (as serological typing is not available) and a lack of longitudinal data to explore stability of antigen prevalence over time. CONCLUSIONS: Neonatal sepsis is associated with diverse K and O types, with substantial geographic and temporal variation even after adjusting for localised transmission clusters. Despite this, a single 20-valent K vaccine could theoretically cover >/=70% of infections in all target regions. Locally-targeted vaccines could achieve higher coverage with lower valency, but are less feasible. In principle, very high coverage could be achieved with lower valency O-based vaccines, however, the protective efficacy against disease of antibodies targeting the O antigen remains uncertain. Further research is needed on cross-reactivity, antigen exposure, and stability of antigens over time, to better inform vaccine development.
