Preimmunization correlates of protection shared across malaria vaccine trials in adults

AbstractIdentifying preimmunization biological characteristics that promote an effective vaccine response offers opportunities for illuminating the critical immunological mechanisms that confer vaccine-induced protection, for developing adjuvant strategies, and for tailoring vaccination regimens to individuals or groups. In the context of malaria vaccine research, studying preimmunization correlates of protection can help address the need for a widely effective malaria vaccine, which remains elusive. In this study, common preimmunization correlates of protection were identified using transcriptomic data from four independent, heterogeneous malaria vaccine trials in adults. Systems-based analyses showed that a moderately elevated inflammatory state prior to immunization was associated with protection against malaria challenge. Functional profiling of protection-associated genes revealed the importance of several inflammatory pathways, including TLR signaling. These findings, which echo previous studies that associated enhanced preimmunization inflammation with protection, illuminate common baseline characteristics that set the stage for an effective vaccine response across diverse malaria vaccine strategies in adults.

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Preimmunization correlates of protection shared across malaria vaccine trials in adults

10.1101/2021.08.13.21262031 ◽

2021 ◽

Author(s):

Maxwell L Neal ◽

Fergal J Duffy ◽

Ying Du ◽

John D Aitchison ◽

Kenneth D Stuart

Keyword(s):

Malaria Vaccine ◽

Effective Vaccine ◽

Vaccine Response ◽

Correlates Of Protection ◽

Vaccine Trials ◽

Or Groups ◽

Immunological Mechanisms ◽

Functional Profiling ◽

Inflammatory State ◽

Baseline Characteristics

Identifying preimmunization biological characteristics that promote an effective vaccine response offers opportunities for illuminating the critical immunological mechanisms that confer vaccine-induced protection, for developing adjuvant strategies, and for tailoring vaccination regimens to individuals or groups. In the context of malaria vaccine research, studying preimmunization correlates of protection can help address the need for a widely-effective malaria vaccine, which remains elusive. In this study, common preimmunization correlates of protection were identified using transcriptomic data from four independent, heterogeneous malaria vaccine trials in adults. Systems-based analyses showed that a moderately elevated inflammatory state prior to immunization was associated with protection against malaria challenge. Functional profiling of protection-associated genes revealed the importance of several inflammatory pathways, including TLR signaling. These findings, which echo previous studies that associated enhanced preimmunization inflammation with protection, illuminate common baseline characteristics that set the stage for an effective vaccine response across diverse malaria vaccine strategies in adults.

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Epitope-Specific Serological Assays for RSV: Conformation Matters

Vaccines ◽

10.3390/vaccines7010023 ◽

2019 ◽

Vol 7 (1) ◽

pp. 23 ◽

Cited By ~ 11

Author(s):

Emily Phung ◽

Lauren Chang ◽

Kaitlyn Morabito ◽

Masaru Kanekiyo ◽

Man Chen ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Antigenic Site ◽

Immune Monitoring ◽

Effective Vaccine ◽

F Protein ◽

Correlates Of Protection ◽

Vaccine Trials ◽

Antigenic Sites ◽

Syncytial Virus ◽

The Impact

Respiratory syncytial virus (RSV) causes substantial morbidity and mortality in children and older adults. An effective vaccine must elicit neutralizing antibodies targeting the RSV fusion (F) protein, which exists in two major conformations, pre-fusion (pre-F) and post-fusion (post-F). Although 50% of the surface is shared, pre-F contains highly neutralization-sensitive antigenic sites not present on post-F. Recent advancement of several subunit F-based vaccine trials has spurred interest in quantifying and understanding the protective potential of antibodies directed to individual antigenic sites. Monoclonal antibody competition ELISAs are being used to measure these endpoints, but the impact of F conformation and competition from antibodies binding to adjacent antigenic sites has not been thoroughly investigated. Since this information is critical for interpreting clinical trial outcomes and defining serological correlates of protection, we optimized assays to evaluate D25-competing antibodies (DCA) to antigenic site Ø on pre-F, and compared readouts of palivizumab-competing antibodies (PCA) to site II on both pre-F and post-F. We show that antibodies to adjacent antigenic sites can contribute to DCA and PCA readouts, and that cross-competition from non-targeted sites is especially confounding when PCA is measured using a post-F substrate. While measuring DCA and PCA levels may be useful to delineate the role of antibodies targeting the apex and side of the F protein, respectively, the assay limitations and caveats should be considered when conducting immune monitoring during vaccine trials and defining correlates of protection.

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Multi-Omic Data Integration Allows Baseline Immune Signatures to Predict Hepatitis B Vaccine Response in a Small Cohort

Frontiers in Immunology ◽

10.3389/fimmu.2020.578801 ◽

2020 ◽

Vol 11 ◽

Author(s):

Casey P. Shannon ◽

Travis M. Blimkie ◽

Rym Ben-Othman ◽

Nicole Gladish ◽

Nelly Amenyogbe ◽

...

Keyword(s):

Hepatitis B ◽

Vaccine Development ◽

Effective Means ◽

Interaction Network ◽

Effective Vaccine ◽

Molecular Characteristics ◽

Vaccine Response ◽

Hbv Vaccine ◽

Fecal Microbiome ◽

Vaccine Responses

BackgroundVaccination remains one of the most effective means of reducing the burden of infectious diseases globally. Improving our understanding of the molecular basis for effective vaccine response is of paramount importance if we are to ensure the success of future vaccine development efforts.MethodsWe applied cutting edge multi-omics approaches to extensively characterize temporal molecular responses following vaccination with hepatitis B virus (HBV) vaccine. Data were integrated across cellular, epigenomic, transcriptomic, proteomic, and fecal microbiome profiles, and correlated to final HBV antibody titres.ResultsUsing both an unsupervised molecular-interaction network integration method (NetworkAnalyst) and a data-driven integration approach (DIABLO), we uncovered baseline molecular patterns and pathways associated with more effective vaccine responses to HBV. Biological associations were unravelled, with signalling pathways such as JAK-STAT and interleukin signalling, Toll-like receptor cascades, interferon signalling, and Th17 cell differentiation emerging as important pre-vaccination modulators of response.ConclusionThis study provides further evidence that baseline cellular and molecular characteristics of an individual’s immune system influence vaccine responses, and highlights the utility of integrating information across many parallel molecular datasets.

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Effect of Plasmodium yoelii Exposure on Vaccination with the 19-Kilodalton Carboxyl Terminus of Merozoite Surface Protein 1 and Vice Versa and Implications for the Application of a Human Malaria Vaccine

Infection and Immunity ◽

10.1128/iai.01063-08 ◽

2008 ◽

Vol 77 (2) ◽

pp. 817-824 ◽

Cited By ~ 7

Author(s):

Jiraprapa Wipasa ◽

Huji Xu ◽

Xueqin Liu ◽

Chakrit Hirunpetcharat ◽

Anthony Stowers ◽

...

Keyword(s):

Malaria Vaccine ◽

Surface Protein ◽

Merozoite Surface Protein ◽

Plasmodium Yoelii ◽

Natural Immunity ◽

Vaccine Response ◽

Malaria Vaccine Candidate ◽

Current Infection ◽

Antibody Specificities ◽

Original Antigenic Sin

ABSTRACT It is well known that exposure to one antigen can modulate the immune responses that develop following exposure to closely related antigens. It is also known that the composition of the repertoire can be skewed to favor epitopes shared between a current infection and a preceding one, a phenomenon referred to as “original antigenic sin.” It was of interest, therefore, to investigate the antibody response that develops following exposure to the malaria vaccine candidate homologue Plasmodium yoelii MSP119 in mice that had previously experienced malaria infection and vice versa. In this study, preexposure of mice to Plasmodium yoelii elicited native anti-MSP119 antibody responses, which could be boosted by vaccination with recombinant MSP119. Likewise, infection of MSP119-primed mice with P. yoelii led to an increase of anti-MSP119 antibodies. However, this increase was at the expense of antibodies to parasite determinants other than MSP119. This change in the balance of antibody specificities significantly affected the ability of mice to withstand a subsequent infection. These data have particular relevance to the possible outcome of malaria vaccination for those situations where the vaccine response is suboptimal and suggest that suboptimal vaccination may in fact render the ultimate acquisition of natural immunity more difficult.

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Characterization of Malaria Transmission by Anopheles (Diptera: Culicidae) in Western Kenya in Preparation for Malaria Vaccine Trials

Journal of Medical Entomology ◽

10.1093/jmedent/27.4.570 ◽

1990 ◽

Vol 27 (4) ◽

pp. 570-577 ◽

Cited By ~ 61

Author(s):

John C. Beier ◽

Peter V. Perkins ◽

Fred K. Onyango ◽

Thomas P. Gargan ◽

Charles N. Oster ◽

...

Keyword(s):

Malaria Transmission ◽

Malaria Vaccine ◽

Western Kenya ◽

Vaccine Trials

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Malaria Vaccine Trials

Parasitology Today ◽

10.1016/s0169-4758(99)01493-3 ◽

1999 ◽

Vol 15 (8) ◽

pp. 348

Author(s):

David Walliker

Keyword(s):

Malaria Vaccine ◽

Vaccine Trials

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Knowledge of tuberculosis and vaccine trial preparedness in Lima, Peru

The International Journal of Tuberculosis and Lung Disease ◽

10.5588/ijtld.17.0116 ◽

2017 ◽

Vol 21 (12) ◽

pp. 1288-1293 ◽

Cited By ~ 3

Author(s):

E. Shu ◽

M. E. Sobieszczyk ◽

V. G. Sal y Rosas ◽

P. Segura ◽

J. T. Galea ◽

...

Keyword(s):

Risk Factors ◽

High Risk ◽

Vaccine Trial ◽

Effective Vaccine ◽

Willingness To Participate ◽

Tb Control ◽

Household Contacts ◽

Efficacy Trials ◽

Vaccine Trials ◽

Efficacy Studies

SETTING: A safe, effective vaccine would improve tuberculosis (TB) control worldwide. Extensive community engagement will be essential to ensure the interest and participation of populations at highest risk.OBJECTIVE/METHOD: To inform the potential implementation of efficacy studies, we assessed TB knowledge, attitudes towards licensed vaccines and willingness to participate in future TB vaccine efficacy trials among 262 household contacts of 79 recently diagnosed pulmonary TB cases in Lima, Peru.RESULTS: Overall knowledge of TB was low. Only 41.6% of household contacts perceived themselves as being at high risk of acquiring TB. Slightly above half (54.2%) indicated willingness to participate in a TB vaccine trial. After clustered analysis adjusting for homogeneity among families, willingness to enroll was associated with belief that receiving all recommended vaccinations is important (adjusted OR [aOR] 3.28, P = 0.016), desire to know more about TB risk factors and clinical trials (aOR 2.60, P = 0.004), older age (aOR 1.02, P = 0.027) and TB knowledge (aOR 0.05, P = 0.039).CONCLUSION: Barriers to participation in TB vaccine trials exist among individuals at high risk for TB. Targeted education about TB risk factors, TB transmission and education about the clinical trial process will be critical for laying the groundwork for future vaccine trials.

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