Vaccine Targets, Clonal Complexes and Virulence Genes among EOGBS and LOGBS in Denmark, 2019-2022

Background
Streptococcus agalactiae (GBS) in infants causes early-onset disease (EOGBS, day 0-6 of life) and late-onset disease (LOGBS, day 7-89 of life). Especially the virulent serotype III ST17 strain with the hvgA gene is associated with meningitis and sepsis.
Two GBS-vaccines have reached phase II studies in pregnant women.
The GBS6-vaccine targets the six most prevalent serotypes (Ia, Ib, II-V) out of ten known.
The GBS-NN-vaccine targets the N-terminal domain of the alpha-like surface proteins Rib, Alpha, and Alp1-3 (AlpN's).

Aim
This study aimed to determine the dominant GBS serotype/clone, assess hvgA prevalence, and estimate potential vaccine coverage in EOGBS and LOGBS in Denmark from 2019 to 2022.

Methods
GBS isolates cultured from blood or cerebrospinal fluid were analysed by whole-genome-sequencing for genotyping, AlpN-gene detection, multi-locus-sequence-typing (MLST), and detection of hvgA.

Results
Sixthly-one GBS isolates were analysed; 59% from EOGBS (n=36) and 41% from LOGBS (n=25).

EOGBS:
Serotype III was most prevalent (44%), followed by Ia (25%), II (14%), Ib (6%), and IX (6%).
For the AlpN’s, rib was most common (55%), followed by alpha (25%), alp1 (22%) and alp2/3 (3%). Two isolates were negative for AlpN’s (6%).
Fifteen EOGBS isolates (42%) carried the hvgA gene; all serotype III.
ST17 was dominant (39%) in EOGBS; all serotype III and 93% rib-positive.
ST23 was found in 13% of EOGBS; all serotype Ia and alp1-positive.

LOGBS:
Serotype III (64%) was dominant, followed by Ia (24%), and IV (8%), and V (4%).
For the AlpN’s, rib was most common (68%), followed by alp1 (20%) and alpha (4%). Two isolates were negative for all AlpN’s (4%).
15 LOGBS isolates (60%) carried the hvgA gene, all serotype III and rib-positive.
ST17 was dominant (56%) in LOGBS; all serotype III and rib-positive.
ST23 was found in 24% LOGBS; 83% of these were serotype Ia and alp1-positive.

Conclusion
The virulent GBS serotype III ST17 strain with the hvgA gene remains the leading cause of both EOGBS and LOGBS in Denmark. The GBS6- and GBS-NN vaccines are expected to reduce the incidences of EOGBS and LOGBS based on this serotype- and AlpN-distribution.