The immunological basis of susceptibility to nontyphoidal Salmonella bacteraemia among HIV-infected adults in Uganda
Lead Research Organisation:
University of Oxford
Department Name: The Jenner Institute
Abstract
Nontyphoidal strains of Salmonella are a major cause of fatal bloodstream infection in Africa, particularly among young children and people living with HIV/AIDS. These Salmonella infections are difficult to diagnose and antibiotic resistance is an increasing problem, so an effective vaccine against nontyphoidal Salmonella (NTS) has the potential to save many lives. Vaccines currently in development against NTS aim to work by stimulating the production of antibodies to a sugar known as O-antigen which is part of the lipopolysaccharide (LPS) molecule and found on the Salmonella surface. My previous research has shown that some HIV-infected adults in Africa have very high levels of these antibodies which then block killing of the Salmonella bacteria. Hence there is a risk that these vaccines may cause harm to people with HIV.
This project aims to understand the basis for susceptibility to NTS bloodstream infections in HIV-infected Africans, and in particular to understand the phenomenon of blocking antibodies, with a view to designing improved vaccines that will protect HIV-infected groups against NTS. I hypothesise that NTS is present at increased levels in the gut in HIV infection and that because the gut wall does not function properly in these patients, the Salmonella bacteria are able to invade the bloodstream. Here they can go on to cause severe disease and death due to the inability of the immune system to kill these bacteria, because of the presence of blocking levels of antibodies. I hypothesise that the continual movement of Salmonella and Salmonella LPS into the circulation drives the production of these high levels of blocking antibodies, because antibody production is no longer appropriately regulated in HIV infection.
I will test this hypothesis in a group of adults newly-diagnosed with HIV infection in Uganda, studying them for two years after they commence antiretroviral therapy (ART) and comparing them with HIV-uninfected subjects. Incidence of NTS bloodstream infections initially rises when starting ART and then falls, but remains much higher than in HIV-uninfected subjects. Therefore, looking at specific immune parameters with time on ART will help understand which are most relevant to susceptibility to NTS infection. Since compromise of the barrier state of the gut is key to my hypothesis, I will study samples of gut tissue taken at endoscopy, as well as peripheral blood.
First, I will test to see whether NTS is present in the gut of HIV-infected participants and whether it occurs more frequently and at higher levels than in HIV-uninfected controls. Then I will investigate the transfer of Salmonella from the gut to the bloodstream and compare this with the immune status of the gut wall, seeing whether this transfer is associated with loss of particular groups of immune cells known as Th17 and mucosal-associated invariant T (MAIT) cells. Finally, I will study the levels and function of antibodies targeting LPS O-antigen, to determine whether they block or kill Salmonella, comparing them with antibodies to a protein known as flagellin which is also present on the Salmonella surface. I will test whether levels and function of these antibodies associate with changes in the numbers and function of two further groups of immune cells, Tfh and Treg cells, which are infected by HIV and which regulate antibody production.
I will follow changes in these immune parameters in the group of HIV-infected participants over time on ART, and look for associations at time points with known differences in susceptibility to NTS. This will enable me to better understand which factors are most relevant for susceptibility to NTS, the mechanism of susceptibility and production of blocking antibodies, and what vaccine or other therapeutic strategies might best protect HIV-infected populations against NTS.
This project aims to understand the basis for susceptibility to NTS bloodstream infections in HIV-infected Africans, and in particular to understand the phenomenon of blocking antibodies, with a view to designing improved vaccines that will protect HIV-infected groups against NTS. I hypothesise that NTS is present at increased levels in the gut in HIV infection and that because the gut wall does not function properly in these patients, the Salmonella bacteria are able to invade the bloodstream. Here they can go on to cause severe disease and death due to the inability of the immune system to kill these bacteria, because of the presence of blocking levels of antibodies. I hypothesise that the continual movement of Salmonella and Salmonella LPS into the circulation drives the production of these high levels of blocking antibodies, because antibody production is no longer appropriately regulated in HIV infection.
I will test this hypothesis in a group of adults newly-diagnosed with HIV infection in Uganda, studying them for two years after they commence antiretroviral therapy (ART) and comparing them with HIV-uninfected subjects. Incidence of NTS bloodstream infections initially rises when starting ART and then falls, but remains much higher than in HIV-uninfected subjects. Therefore, looking at specific immune parameters with time on ART will help understand which are most relevant to susceptibility to NTS infection. Since compromise of the barrier state of the gut is key to my hypothesis, I will study samples of gut tissue taken at endoscopy, as well as peripheral blood.
First, I will test to see whether NTS is present in the gut of HIV-infected participants and whether it occurs more frequently and at higher levels than in HIV-uninfected controls. Then I will investigate the transfer of Salmonella from the gut to the bloodstream and compare this with the immune status of the gut wall, seeing whether this transfer is associated with loss of particular groups of immune cells known as Th17 and mucosal-associated invariant T (MAIT) cells. Finally, I will study the levels and function of antibodies targeting LPS O-antigen, to determine whether they block or kill Salmonella, comparing them with antibodies to a protein known as flagellin which is also present on the Salmonella surface. I will test whether levels and function of these antibodies associate with changes in the numbers and function of two further groups of immune cells, Tfh and Treg cells, which are infected by HIV and which regulate antibody production.
I will follow changes in these immune parameters in the group of HIV-infected participants over time on ART, and look for associations at time points with known differences in susceptibility to NTS. This will enable me to better understand which factors are most relevant for susceptibility to NTS, the mechanism of susceptibility and production of blocking antibodies, and what vaccine or other therapeutic strategies might best protect HIV-infected populations against NTS.
Technical Summary
Nontyphoidal Salmonellae (NTS) cause fatal bacteraemia among HIV-infected Africans. Surprisingly, susceptibility initially increases on antiretroviral therapy (ART) and, although subsequently diminishes, it remains over 50-fold higher than in HIV-uninfected Africans. Candidate vaccines aim to induce antibodies against Salmonella lipopolysaccharide (LPS) O-antigen. Previously, I found that these antibodies occur in excess in some HIV-infected Africans and block killing of NTS, raising safety concerns.
Blocking antibodies may represent one of a number of factors contributing to susceptibility. I propose an integrated hypothesis that NTS bacteraemia in HIV-infected Africans occurs due to:
1. high levels of NTS in the gastrointestinal (GI) tract,
2. translocation of NTS to the circulation secondary to loss of CD4+ Th17 cells and mucosal-associated invariant T (MAIT) cells,
3. dysregulated production of anti-O-antigen antibodies, secondary to translocated LPS and Tfh cell dysregulation; these antibodies are unable to kill translocated bacteria, resulting in bacteraemia.
The experimental approach exploits the changes in susceptibility to NTS with ART and investigates blood, GI mucosa collected by endoscopy, and stool in a cohort of treatment-naïve HIV-infected adults in Uganda, immediately before and for 24 months after initiating ART, in comparison with HIV-uninfected adults. I will examine Salmonella in the GI tract by metagenomics, and its translocation to the circulation by 16S qPCR, and immunological and biochemical markers. Concentration and function of blocking antibodies will be determined by ELISA and bactericidal assays, while frequency and function of T cell subsets, focusing on CD4+ Th17 and Tfh, and MAIT cells, will be explored by flow cytometry. I will test for association between these parameters and findings will be correlated with time on ART. The detailed knowledge obtained will help guide the development of appropriate vaccines and therapies.
Blocking antibodies may represent one of a number of factors contributing to susceptibility. I propose an integrated hypothesis that NTS bacteraemia in HIV-infected Africans occurs due to:
1. high levels of NTS in the gastrointestinal (GI) tract,
2. translocation of NTS to the circulation secondary to loss of CD4+ Th17 cells and mucosal-associated invariant T (MAIT) cells,
3. dysregulated production of anti-O-antigen antibodies, secondary to translocated LPS and Tfh cell dysregulation; these antibodies are unable to kill translocated bacteria, resulting in bacteraemia.
The experimental approach exploits the changes in susceptibility to NTS with ART and investigates blood, GI mucosa collected by endoscopy, and stool in a cohort of treatment-naïve HIV-infected adults in Uganda, immediately before and for 24 months after initiating ART, in comparison with HIV-uninfected adults. I will examine Salmonella in the GI tract by metagenomics, and its translocation to the circulation by 16S qPCR, and immunological and biochemical markers. Concentration and function of blocking antibodies will be determined by ELISA and bactericidal assays, while frequency and function of T cell subsets, focusing on CD4+ Th17 and Tfh, and MAIT cells, will be explored by flow cytometry. I will test for association between these parameters and findings will be correlated with time on ART. The detailed knowledge obtained will help guide the development of appropriate vaccines and therapies.
Planned Impact
The Global Health Vaccine Industry
By seeking to understand the immunological basis of susceptibility to NTS bacteraemia in HIV-infected Africans, the study addresses a key question for the global health vaccine community engaged in developing vaccines against NTS, including the GSK Vaccines Institute for Global Health, Siena, and the Center for Vaccine Development, University of Maryland. NTS bacteraemia in African adults is a major cause of morbidity and mortality. Following our previous finding of excess blocking levels of antibodies to Salmonella LPS O-antigen in some HIV-infected Africans, there is major uncertainty as to whether NTS vaccines currently in development and designed to induce such antibodies with be beneficial, harmful or have no effect in HIV-infected groups. Study findings will help indicate whether an alternative vaccine approach is required and/or possible to protect HIV-infected populations against NTS. With current vaccines in development due to be tested in clinical trials during the lifetime of the fellowship, this project is particularly timely and would have immediate impact. An improved vaccine approach that protects HIV-infected people, as well as immune-naïve children, will have a significantly broader impact in relation to global burden of disease than vaccine approaches that only protect the latter group.
Health policy makers
As the research will inform global health policy makers concerning the potential of NTS vaccines in development for protecting HIV-infected individuals against invasive NTS (iNTS) disease, it will help indicate what high-level direction is indicated regarding the development of alternative vaccine strategies. Our findings will help understand why HIV-infected patients in Africa become more susceptible to iNTS during the first three months on ART, and why, following immune reconstitution, they remain far more susceptible than HIV-uninfected adults. This is important for guiding strategies other than vaccination, such as nutritional and anti-microbial interventions, to prevent iNTS disease in this population and will have implications for understanding other causes of morbidity and mortality among HIV-infected subjects receiving ART.
Clinical researchers
The work will be of interest and benefit to clinical researchers spanning disciplines of immunology, microbiology, infectious disease, gastroenterology and HIV medicine, as well as vaccinology, as described in the 'Academic beneficiaries' section.
HIV-infected population
The HIV/AIDS community takes great interest in clinical research related to HIV infection and the work will be of interest to this group, and will help inform, in addition to the potential benefit of vaccines in development, what self-action may be beneficial in relation to minimising risk of Salmonella disease and which HIV-infected sub-groups of patients are most susceptible to NTS. As mentioned above, translation of the findings of this project into improved NTS vaccine design has the potential, over around a ten year time frame, to have major impact in terms of decreased morbidity and mortality from NTS disease among Africans living with HIV/AIDS.
Project staff
Finally, a project with this broad cross-discipline approach, and study of clinical material in the developing world, provides excellent opportunities for members of the study team in Oxford and Entebbe to increase their range of skills and expertise. This learning will be enhanced by the opportunities to learn from world-leading collaborators and specific workshops, and to attend training at Oxford and MRC/UVRI Uganda.
By seeking to understand the immunological basis of susceptibility to NTS bacteraemia in HIV-infected Africans, the study addresses a key question for the global health vaccine community engaged in developing vaccines against NTS, including the GSK Vaccines Institute for Global Health, Siena, and the Center for Vaccine Development, University of Maryland. NTS bacteraemia in African adults is a major cause of morbidity and mortality. Following our previous finding of excess blocking levels of antibodies to Salmonella LPS O-antigen in some HIV-infected Africans, there is major uncertainty as to whether NTS vaccines currently in development and designed to induce such antibodies with be beneficial, harmful or have no effect in HIV-infected groups. Study findings will help indicate whether an alternative vaccine approach is required and/or possible to protect HIV-infected populations against NTS. With current vaccines in development due to be tested in clinical trials during the lifetime of the fellowship, this project is particularly timely and would have immediate impact. An improved vaccine approach that protects HIV-infected people, as well as immune-naïve children, will have a significantly broader impact in relation to global burden of disease than vaccine approaches that only protect the latter group.
Health policy makers
As the research will inform global health policy makers concerning the potential of NTS vaccines in development for protecting HIV-infected individuals against invasive NTS (iNTS) disease, it will help indicate what high-level direction is indicated regarding the development of alternative vaccine strategies. Our findings will help understand why HIV-infected patients in Africa become more susceptible to iNTS during the first three months on ART, and why, following immune reconstitution, they remain far more susceptible than HIV-uninfected adults. This is important for guiding strategies other than vaccination, such as nutritional and anti-microbial interventions, to prevent iNTS disease in this population and will have implications for understanding other causes of morbidity and mortality among HIV-infected subjects receiving ART.
Clinical researchers
The work will be of interest and benefit to clinical researchers spanning disciplines of immunology, microbiology, infectious disease, gastroenterology and HIV medicine, as well as vaccinology, as described in the 'Academic beneficiaries' section.
HIV-infected population
The HIV/AIDS community takes great interest in clinical research related to HIV infection and the work will be of interest to this group, and will help inform, in addition to the potential benefit of vaccines in development, what self-action may be beneficial in relation to minimising risk of Salmonella disease and which HIV-infected sub-groups of patients are most susceptible to NTS. As mentioned above, translation of the findings of this project into improved NTS vaccine design has the potential, over around a ten year time frame, to have major impact in terms of decreased morbidity and mortality from NTS disease among Africans living with HIV/AIDS.
Project staff
Finally, a project with this broad cross-discipline approach, and study of clinical material in the developing world, provides excellent opportunities for members of the study team in Oxford and Entebbe to increase their range of skills and expertise. This learning will be enhanced by the opportunities to learn from world-leading collaborators and specific workshops, and to attend training at Oxford and MRC/UVRI Uganda.
Organisations
- University of Oxford (Fellow, Lead Research Organisation)
- PUBLIC HEALTH ENGLAND (Collaboration)
- University of Toronto (Collaboration)
- University of Massachusetts (Collaboration)
- National Institute for Biological Standards and Control (NIBSC) (Collaboration)
- UNIVERSITY HOSPITALS BIRMINGHAM NHS FOUNDATION TRUST (Collaboration)
People |
ORCID iD |
Calman MacLennan (Principal Investigator / Fellow) |
Publications
![publication icon](/resources/img/placeholder-60x60.png)
MacLennan CA
(2023)
Salmonella Combination Vaccines: Moving Beyond Typhoid.
in Open forum infectious diseases
![publication icon](/resources/img/placeholder-60x60.png)
![publication icon](/resources/img/placeholder-60x60.png)
Stefanetti G
(2022)
Impact and Control of Sugar Size in Glycoconjugate Vaccines.
in Molecules (Basel, Switzerland)
![publication icon](/resources/img/placeholder-60x60.png)
MacLennan CA
(2021)
The Background, Role and Approach for Development of a Controlled Human Infection Model for Nontyphoidal Salmonella.
in Current topics in microbiology and immunology
![publication icon](/resources/img/placeholder-60x60.png)
![publication icon](/resources/img/placeholder-60x60.png)
Gottlieb.S
(2021)
Preferred product characteristics for gonococcal vaccines
![publication icon](/resources/img/placeholder-60x60.png)
Gilchrist J
(2021)
The immunology of infection
in Medicine
![publication icon](/resources/img/placeholder-60x60.png)
Domínguez-Medina CC
(2020)
Outer membrane protein size and LPS O-antigen define protective antibody targeting to the Salmonella surface.
in Nature communications
![publication icon](/resources/img/placeholder-60x60.png)
Micoli F
(2020)
Short Vi-polysaccharide abrogates T-independent immune response and hyporesponsiveness elicited by long Vi-CRM 197 conjugate vaccine
in Proceedings of the National Academy of Sciences
![publication icon](/resources/img/placeholder-60x60.png)
Steele AD
(2020)
Typhoid Conjugate Vaccines and Enteric Fever Control: Where to Next?
in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
![publication icon](/resources/img/placeholder-60x60.png)
![publication icon](/resources/img/placeholder-60x60.png)
Micoli F
(2020)
Outer membrane vesicle vaccines.
in Seminars in immunology
![publication icon](/resources/img/placeholder-60x60.png)
Benedikz EK
(2019)
Bacterial flagellin promotes viral entry via an NF-kB and Toll Like Receptor 5 dependent pathway.
in Scientific reports
![publication icon](/resources/img/placeholder-60x60.png)
Diallo K
(2019)
Genomic characterization of novel Neisseria species.
in Scientific reports
![publication icon](/resources/img/placeholder-60x60.png)
Kaminski RW
(2019)
Consensus Report on Shigella Controlled Human Infection Model: Immunological Assays.
in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
![publication icon](/resources/img/placeholder-60x60.png)
Stockdale L
(2019)
Cross-sectional study of IgG antibody levels to invasive nontyphoidal Salmonella LPS O-antigen with age in Uganda.
in Gates open research
![publication icon](/resources/img/placeholder-60x60.png)
Park SE
(2019)
The Severe Typhoid Fever in Africa Program: Study Design and Methodology to Assess Disease Severity, Host Immunity, and Carriage Associated With Invasive Salmonellosis.
in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
![publication icon](/resources/img/placeholder-60x60.png)
MacLennan CA
(2019)
Consensus Report on Shigella Controlled Human Infection Model: Clinical Endpoints.
in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
![publication icon](/resources/img/placeholder-60x60.png)
![publication icon](/resources/img/placeholder-60x60.png)
Talaat KR
(2019)
Consensus Report on Shigella Controlled Human Infection Model: Conduct of Studies.
in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
![publication icon](/resources/img/placeholder-60x60.png)
![publication icon](/resources/img/placeholder-60x60.png)
MacLennan CA
(2019)
Consensus Report on Shigella Controlled Human Infection Model: Introduction and Overview.
in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
![publication icon](/resources/img/placeholder-60x60.png)
Gilchrist JJ
(2019)
Invasive Nontyphoidal Salmonella Disease in Africa.
in EcoSal Plus
![publication icon](/resources/img/placeholder-60x60.png)
Rossi O
(2019)
The essential role of complement in antibody-mediated resistance to Salmonella.
in Immunology
Description | Successful preclinical proof of concept for candidate gonococcal native outer membrane vesicle vaccine |
Exploitation Route | Proof of concept for use of native outer membrane vesicle platform as a promising approach to developing vaccines against gonorrhoea and AMR |
Sectors | Pharmaceuticals and Medical Biotechnology |
Description | WHO Gonococcal Vaccines Preferred Product Characteristics document |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Participation in a guidance/advisory committee |
URL | https://www.who.int/immunization/research/ppc-tpp/Gonococcal_vaccine_PPCs_for-public-comment.pdf |
Description | GonoVac A vaccine to prevent gonorrhea and combat spread of AMR targeting LMICs |
Amount | £36,000 (GBP) |
Funding ID | 0011555 |
Organisation | Medical and Life Sciences Translational Fund |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 12/2021 |
End | 03/2022 |
Description | The Gonococcal Vaccine Project |
Amount | £60,000 (GBP) |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 01/2021 |
End | 08/2022 |
Description | Translational development of an outer membrane vesicle vaccine against gonorrhoea' |
Amount | £47,134 (GBP) |
Funding ID | 0009939 |
Organisation | Medical and Life Sciences Translational Fund |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 11/2020 |
End | 03/2021 |
Description | dmGC_0817560 NOMV' to develop a gonococcal native OMV vaccine to phase 1 clinical trial |
Amount | $7,268,507 (USD) |
Funding ID | 4500003783 |
Organisation | Biomedical Advanced Research and Development Authority |
Sector | Public |
Country | United States |
Start | 01/2021 |
End | 08/2024 |
Title | Antibody-depleted human serum for bactericidal assays |
Description | We developed an adsorption method to prepare specific antibody-depleted normal human serum as a source of complement for human serum bactericidal assays for Salmonella |
Type Of Material | Technology assay or reagent |
Year Produced | 2021 |
Provided To Others? | Yes |
Impact | Publication: Siggins MK, MacLennan CA. An adsorption method to prepare specific antibody-depleted normal human serum as a source of complement for human serum bactericidal assays for Salmonella. Vaccine 2021 Dec 17;39(51):7503-7509. doi: 10.1016/j.vaccine.2021.10.023. Epub 2021 Nov 15. PMID: 34794820 |
Description | NIBSC/MHRA partnership on diagnostic assays |
Organisation | National Institute for Biological Standards and Control (NIBSC) |
Country | United Kingdom |
PI Contribution | Collaboration on development of assays to assess vaccine reactogenicity (monocyte activation test) and vaccine potency (antigenicity ELISA) to reduce experimental animal use. |
Collaborator Contribution | Collaboration on development of assays to assess vaccine reactogenicity (monocyte activation test) and vaccine potency (antigenicity ELISA) to reduce experimental animal use. |
Impact | None yet |
Start Year | 2020 |
Description | Oxford/Massachusetts Gonococcal Vaccine collaboration |
Organisation | University of Massachusetts |
Country | United States |
Sector | Academic/University |
PI Contribution | Design and development of innovating vaccines using native outer membrane vesicles against gonococcus |
Collaborator Contribution | Assessment of preclinical efficacy of gonococcal vaccine candidate. Provided preclinical proof of concept facilitating successful application for substantive funding from CARB-X. |
Impact | Substantive grant funding from CARB-X |
Start Year | 2018 |
Description | Oxford/University of Toronto Gonococcal Vaccine Collaboration |
Organisation | University of Toronto |
Country | Canada |
Sector | Academic/University |
PI Contribution | Collaboration on gonococcal vaccines |
Collaborator Contribution | Collaboration on gonococcal biology and gonococcal animal challenge studies |
Impact | too early |
Start Year | 2022 |
Description | Oxford/University of Toronto Gonococcal Vaccine Collaboration |
Organisation | University of Toronto |
Country | Canada |
Sector | Academic/University |
PI Contribution | Collaboration on gonococcal vaccines |
Collaborator Contribution | Collaboration on gonococcal biology and gonococcal animal challenge studies |
Impact | too early |
Start Year | 2022 |
Description | Public Health England/Porton Down Gonococcal Serum Bactericidal Assay Collaboration |
Organisation | Public Health England |
Department | Public Health England Porton Down |
Country | United Kingdom |
Sector | Public |
PI Contribution | Gonococcal vaccine development and access to animal and clinical samples following exposure to gonococcus |
Collaborator Contribution | Development of a serum bactericidal assay for determination of functional antibody responses to gonococcus |
Impact | too early |
Start Year | 2021 |
Description | University Hospital Birmingham Human Immunity to Gonorrhoea |
Organisation | University Hospitals Birmingham NHS Foundation Trust |
Country | United Kingdom |
Sector | Public |
PI Contribution | Application of principles of gonococcal immunology to the understanding of correlates of protection against gonorrhoea in humans |
Collaborator Contribution | Clinical expertise in gonorrhoea. Access to clinical samples from individuals attending genito-urinary medicine clinics with and without gonorrhoea. |
Impact | too early |
Start Year | 2021 |
Title | Gonococcal candidate vaccine dmGC_0817560 NOMV |
Description | The medical product is an innovative native outer membrane vesicle vaccine against gonorrhoea and antimicrobial resistance. It completed preclinical proof of concept in 2019, accelerating clearance of gonococcus from the mouse gonococcal infection model. On the basis of this work, substantive funding was secured from CARB-X which will take the vaccine through a stage-gated pathway to a phase 1 clinical trial. It is currently in Lead Optimisation Stage. It has previously received funding from a Wellcome Pathfinder Award and BactiVac Catalyst Funding Award |
Type | Therapeutic Intervention - Vaccines |
Current Stage Of Development | Refinement. Non-clinical |
Year Development Stage Completed | 2021 |
Development Status | Under active development/distribution |
Impact | The vaccine is one of a leading group of new candidates against gonorrhoea |
Description | Oral presentation at World Vaccine Congress Barcelona 2021 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Industry/Business |
Results and Impact | Presentation on gonococcal vaccine development at the World Vaccine Congress |
Year(s) Of Engagement Activity | 2021 |
URL | https://www.terrapinn.com/conference/world-vaccine-congress-europe/Conference.stm |