Streptococcus agalactiae (Group B streptococcus or GBS) is a leading cause of neonatal and infant sepsis and meningitis globally.  GBS is associated with maternal sepsis, stillbirths and preterm births, and can cause disease in immunocompromised adults and the elderly, but the highest incidence of all is in neonates and young infants up to age 3 months. GBS was estimated to have caused 319,000 cases of neonatal disease annually (2015), resulting in 90 000 deaths and at least 57,000 stillbirths [1].  The highest burden is in Africa, where 54% of estimated invasive GBS cases, and 65% of all fetal/infant deaths occur. 

An average of 18% (with regional variation) of pregnant women carry GBS worldwide [2]. Administration of intrapartum antibiotic prophylaxis (IAP) to pregnant women with GBS colonization can substantially reduce the incidence of early-onset GBS disease, but IAP does not prevent late-onset GBS disease, which in most cases are transmitted postnatally. Moreover, this strategy is not feasible in many lower- and middle-income countries (LMIC), where both antibiotics and systematic GBS screenings may not be readily available.  Since GBS occurs too early in life for neonates and infants to elicit an effective immune response following vaccination, an effective maternal GBS vaccine targeting pregnant women offers the potential to protect infants against both early- and late-onset GBS disease through transplacental transfer of maternal antibodies, and reduce disease burden worldwide.

The development of Group B Streptococcus (GBS) vaccines for maternal immunization has been identified by the Product Development for Vaccines Advisory Committee (PDVAC) as a priority, because of the major public health burden posed by GBS in LMIC. 

WHO Preferred Product Characteristics (PPCs) aim to discuss and present preferences relative to vaccine parameters that are important when considering the public health need and the pathway to policy decision and use. The strategic goal for GBS vaccines is to develop and license safe, effective and affordable GBS vaccines for maternal immunization during pregnancy to prevent GBS-related stillbirth and invasive GBS disease in neonates and young infants, appropriate for use in high-, middle- and low-income countries. PPCs for GBS vaccines can be accessed below.

Vaccine development technology roadmaps aim to highlight priority activities for vaccine researchers, funders and product developers, with the goal to accelerate the pathway to availability. 

A Vaccine Development Technology Roadmap for GBS vaccines can be accessed below.

GBS are divided into ten serotypes based on capsular polysaccharide (CPS) antigens expressed, and five of the serotypes (Ia, Ib, II, III and V) account for the vast majority of the disease. Antibody levels against CPS in pregnant women and the risk of invasive GBS disease in their infants have been shown to be inversely related, leading to the development of several multivalent GBS CPS protein-conjugate vaccine candidates [3].

There are also several surface proteins, including the alpha-like proteins, that have been associated with protection against infant disease. Six members of the family exists: Rib, Alpha C, and Alp 1–4 [4]. Naturally acquired antibodies against the Alp proteins appear to exist in most individuals, and Alpha C and Rib specific antibody levels correlate inversely with increased risk of neonatal infection [5]. Whereas similar correlations have not yet been described for the other Alps, immunization experiments in animals have demonstrated a protective role for antibodies also against Alp3 [6]. Combined with the considerable homology between the different Alp genes, this indicates that all Alp family members are relevant targets for protective immunity. 

Efficacy studies for GBS vaccine will require a large number of participants, therefore initial vaccine licensure based on immunological correlates of protection (CoP) should be explored, followed by post licensure studies to assess effectiveness and to evaluate the reduction in disease burden.  WHO is engaged in discussions to support the establishment of a CoP which may be used as a basis for licensure.

Roadmap 

1. A.C. Seale, F. Bianchi-Jassir, N.J. Russell, M. Kohli-Lynch, C.J. Tann, J. Hall, et al. Estimates of the Burden of Group B Streptococcal Disease Worldwide for Pregnant Women, Stillbirths, and Children Clin Infect Dis, 65 (suppl_2) (2017) S200–s19
2. Russell NJ, Seale AC, O’Driscoll M, O’Sullivan C, Bianchi-Jassir F, Gonzalez-Guarin J, et al. Maternal Colonization With Group B Streptococcus and Serotype Distribution Worldwide: Systematic Review and Meta-analyses. Clin Infect Dis Off Publ Infect Dis Soc Am. 2017;65: S100–S111. pmid:29117327
3. Kobayashi M, Vekemans J, Baker CJ, Ratner AJ, Le Doare K, Schrag SJ. Group B streptococcus vaccine development: present status and future considerations, with emphasis on perspectives for low and middle income countries. F1000Res 2016; 5:2355.
4. J.A. Maeland, J.E. Afset, R.V. Lyng, A. Radtke. Survey of immunological features of the alpha-like proteins of Streptococcus agalactiae. Clin Vaccine Immunol, 22 (2015), pp. 153-159.
5. C. Larsson, M. Lindroth, P. Nordin, M. Stalhammar-Carlemalm, G. Lindahl, I. Krantz. Association between low concentrations of antibodies to protein alpha and Rib and invasive neonatal group B streptococcal infection. Arch Dis Child Fetal Neonatal Ed, 91 (2006), pp. F403-F408
6. H.H. Yang, S.J. Mascuch, L.C. Madoff, L.C. Paoletti. Recombinant group B Streptococcus alpha-like protein 3 is an effective immunogen and carrier protein. Clin Vaccine Immunol, 15 (2008), pp. 1035-1041

Updated April 30, 2022