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Development of experimental GBS vaccine for mucosal immunization.

ABSTRACT: Streptococcus agalactiae, or group B streptococcus (GBS), is an important pathogen as it is the leading cause of neonatal deaths due to sepsis, meningitis or bacterial pneumonia. Although the development of an effective and safe GBS vaccine is on the agenda of many research labs, there is no GBS vaccine on the market yet. In the present study we attempted to engineer a live vaccine strain based on Bac, a surface protein of GBS, incorporated into a surface fimbrial protein of probiotic Enterococcus. The resulting strain induced specific systemic and local immune responses in mice and provided protection against GBS when administered via the intranasal, oral or intravaginal immunization routes.

SUBMITTER: Gupalova T

PROVIDER: S-EPMC5935385 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Development of experimental GBS vaccine for mucosal immunization.

Gupalova T T Leontieva G G Kramskaya T T Grabovskaya K K Bormotova E E Korjevski D D Suvorov A A

PloS one 20180504 5

Streptococcus agalactiae, or group B streptococcus (GBS), is an important pathogen as it is the leading cause of neonatal deaths due to sepsis, meningitis or bacterial pneumonia. Although the development of an effective and safe GBS vaccine is on the agenda of many research labs, there is no GBS vaccine on the market yet. In the present study we attempted to engineer a live vaccine strain based on Bac, a surface protein of GBS, incorporated into a surface fimbrial protein of probiotic Enterococc ...[more]

PMID: 29727446

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Project description:Respiratory syncytial virus (RSV) infections are the leading cause of severe respiratory illness in early infancy. Although the majority of children and adults mount immune responses against RSV, recurrent infections are frequent throughout life. Humoral and cellular responses contribute to an effective immunity but also their localization at respiratory mucosae is increasingly recognized as an important factor. In the present study, we evaluate a mucosal vaccine based on an adenoviral vector encoding for the RSV fusion protein (Ad-F), and we investigate two genetic adjuvant candidates that encode for Interleukin (IL)-1β and IFN-β promoter stimulator I (IPS-1), respectively. While vaccination with Ad-F alone was immunogenic, the inclusion of Ad-IL-1β increased F-specific mucosal immunoglobulin A (IgA) and tissue-resident memory T cells (TRM). Consequently, immunization with Ad-F led to some control of virus replication upon RSV infection, but Ad-F+Ad-IL-1β was the most effective vaccine strategy in limiting viral load and weight loss. Subsequently, we compared the Ad-F+Ad-IL-1β-induced immunity with that provoked by a primary RSV infection. Systemic F-specific antibody responses were higher in immunized than in previously infected mice. However, the primary infection provoked glycoprotein G-specific antibodies as well eventually leading to similar neutralization titers in both groups. In contrast, mucosal antibody levels were low after infection, whereas mucosal immunization raised robust F-specific responses including IgA. Similarly, vaccination generated F-specific TRM more efficiently compared to a primary RSV infection. Although the primary infection resulted in matrix protein 2 (M2)-specific T cells as well, they did not reach levels of F-specific immunity in the vaccinated group. Moreover, the infection-induced T cell response was less biased towards TRM compared to vaccine-induced immunity. Finally, our vaccine candidate provided superior protection against RSV infection compared to a primary infection as indicated by reduced weight loss, virus replication, and tissue damage. In conclusion, our mucosal vaccine candidate Ad-F+Ad-IL-1β elicits stronger mucosal immune responses and a more effective protection against RSV infection than natural immunity generated by a previous infection. Harnessing mucosal immune responses by next-generation vaccines is therefore a promising option to establish effective RSV immunity and thereby tackle a major cause of infant hospitalization.

Project description:BackgroundA maternal group B streptococcal (GBS) vaccine could prevent neonatal sepsis and meningitis. Its cost-effectiveness in low-income sub-Saharan Africa, a high burden region, is unknown.MethodsWe used a decision tree model, with Markov nodes to project infants' lifetimes, to compare maternal immunization delivered through routine antenatal care with no immunization. 37 countries were clustered on the basis of economic and health resources and past public health performance. Vaccine efficacy for covered serotypes was ranged from 50% to 90%. The model projected EOGBS (early-onset) and LOGBS (late-onset) cases and deaths, disability-adjusted life years (DALYs), healthcare costs (2014 US$), and cost-effectiveness for a representative country in each of the four clusters: Guinea-Bissau, Uganda, Nigeria, and Ghana. Maximum vaccination costs/dose were estimated to meet two cost-effectiveness benchmarks, 0.5 GDP and GDP per capita/DALY, for ranges of disease incidence (reported and adjusted for under-reporting) and vaccine efficacy.ResultsAt coverage equal to the proportion of pregnant women with?4 antenatal visits (ANC4) and serotype-specific vaccine efficacy of 70%, maternal GBS immunization would prevent one-third of GBS cases and deaths in Uganda and Nigeria, where ANC4 is 50%, 42-43% in Guinea-Bissau (ANC4=65%), and 55-57% in Ghana (ANC4=87%). At a vaccination cost of $7/dose, maternal immunization would cost $320-$350/DALY averted in Guinea-Bissau, Nigeria, and Ghana, less than half these countries' GDP per capita. In Uganda, which has the lowest case fatality ratios, the cost would be $573/DALY. If the vaccine prevents a small proportion of stillbirths, it would be even more cost-effective. Vaccination cost/dose, disease incidence, and case fatality were key drivers of cost/DALY in sensitivity analyses.ConclusionMaternal GBS immunization could be a cost-effective intervention in low-income sub-Saharan Africa, with cost-effectiveness ratios similar to other recently introduced vaccines. The vaccination cost at which introduction is cost-effective depends on disease incidence and vaccine efficacy. Clinical Trial registry name and registration number: Not applicable.

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Development of experimental GBS vaccine for mucosal immunization.

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Development of experimental GBS vaccine for mucosal immunization.

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