Recent updates on correlates of vaccine-induced protection

Plotkin, Stanley А.

doi:10.3389/fimmu.2022.1081107

Cited by 25 publications

(21 citation statements)

References 71 publications

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“…Pathogen-neutralizing antibodies are generally accepted as a correlate of protection for most vaccine-preventable infections, 13 , 14 and virus-neutralizing IgG has been shown to be protective against SARS-CoV-2 infection. 15–17 Elicitation of protective levels of mucosal IgA by mRNA-based vaccines administered via injection has not been reported.…”

Section: Discussionmentioning

confidence: 99%

Serological assessment of the durability of vaccine-mediated protection against SARS-CoV-2 infection

Bates,

Lirette,

Farmer

et al. 2024

Human Vaccines & Immunotherapeutics

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Virus-neutralizing antibodies are often accepted as a correlate of protection against infection, though questions remain about which components of the immune response protect against SARS-CoV-2 infection. In this small observational study, we longitudinally measured spike receptor binding domain (RBD)-specific and nucleocapsid (NP)-specific serum IgG in a human cohort immunized with the Pfizer BNT162b2 vaccine. NP is not encoded in the vaccine, so an NP-specific response is serological evidence of natural infection. A greater than fourfold increase in NP-specific antibodies was used as the serological marker of infection. Using the RBD-specific IgG titers prior to seroconversion for NP, we calculated a protective threshold for RBD-specific IgG. On average, the RBD-specific IgG response wanes below the protective threshold 169 days following vaccination. Many participants without a history of a positive test result for SARS-CoV-2 infection seroconverted for NP-specific IgG. As a group, participants who seroconverted for NP-specific IgG had significantly higher levels of RBD-specific IgG following NP-seroconversion. RBD-specific IgG titers may serve as one correlate of protection against SARS-CoV-2 infection. These titers wane below the proposed protective threshold approximately six months following immunization. Based on serological evidence of infection, the frequency of breakthrough infections and consequently the level of SARS-CoV-2-specific immunity in the population may be higher than what is predicted based on the frequency of documented infections.

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Section: Discussionmentioning

confidence: 99%

Serological assessment of the durability of vaccine-mediated protection against SARS-CoV-2 infection

Bates,

Lirette,

Farmer

et al. 2024

Human Vaccines & Immunotherapeutics

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“…The application of surrogates of protection for licensure of vaccine candidates has been extensively used for vaccines against meningitis, pneumococcal and in uenza, to mention a few. 40 However, establishing a CoP for many infectious diseases can be extremely complex and to date, there is no accepted CoP for shigellosis. Qin et al de ne CoPs as immunological measurements that predict a vaccine's level of protective e cacy based on differences between the vaccinated and unvaccinated groups.…”

Section: Discussionmentioning

confidence: 99%

Towards establishing correlates of protection against shigellosis: assessing immunological endpoints across immune responses to the Shigella sonnei Generalized Modules for Membrane Antigens (GMMA) candidate vaccine (1790GAHB).

Nakakana,

Conti,

Rossi

et al. 2023

Preprint

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Shigella spp. are a leading bacterial cause of diarrhea. No widely licensed vaccines are available and there is no generally accepted correlate of protection. We tested a S. sonnei Generalized Modules for Membrane Antigen (GMMA)-based vaccine (1790GAHB) in a phase 2b, placebo-controlled, randomized, controlled human infection model study (NCT03527173) enrolling healthy United States adults aged 18–50 years. We report analyses evaluating immune responses to vaccination, with the aim to identify correlates of risk for shigellosis among assessed immunomarkers. We found that 1790GAHB elicited S. sonnei lipopolysaccharide specific α4β7+ immunoglobulin (Ig) G and IgA secreting B cells which are likely homing to the gut, indicating the ability to induce a mucosal in addition to a systemic response, despite parenteral delivery. We were unable to establish or confirm threshold levels that predict vaccine efficacy facilitating the evaluation of vaccine candidates. However, serum anti-lipopolysaccharide IgG and bactericidal activity were identified as potential correlates of risk for shigellosis.

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“…They are a key receptor in the immune system (Nicholson 2016) and genetic variation drives the humoral adaptive immune response in vaccination, infection, and autoimmunity (Mikocziova et al 2021). Due to this importance, antibodies are actively being researched to understand their correlates of protection for various diseases (Huang et al 2020) (Plotkin 2023) and ability to neutralize pathogens (Gumah Ali et al 2020), to utilize antibody indexes to diagnose viral infections (Shamier et al 2021), to apply them to various types of imaging (Rodriguez et al 2022) (Im et al 2019), and to engineer immunotherapeutics for a wide variety of pathologies, such as cancers (Scott et al 2012) (Zinn et al 2023; Lucas et al 2021) and autoimmune diseases (Carter and Rajpal 2022). Research into understanding and engineering antibody binding is largely focused on their Complementary Determining Regions (CDRs), hypervariable regions that predominantly determine their binding repertoires (Peng et al 2022) (Chiu et al 2019).…”

Section: Introductionmentioning

confidence: 99%

A Comparison of Antibody-Antigen Complex Sequence-to-Structure Prediction Methods and their Systematic Biases

McCoy,

Ackerman,

Grigoryan

2024

Preprint

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The ability to accurately predict antibody-antigen complex structures from their sequences could greatly advance our understanding of the immune system and would aid in the development of novel antibody therapeutics. There have been considerable recent advancements in predicting protein-protein interactions (PPIs) fueled by progress in machine learning (ML). To understand the current state of the field, we compare six representative methods for predicting antibody-antigen complexes from sequence, including two deep learning approaches trained to predict PPIs in general (AlphaFold-Multimer, RoseTTAFold), two composite methods that initially predict antibody and antigen structures separately and dock them (using antibody-mode ClusPro), local refinement in Rosetta (SnugDock) of globally docked poses from ClusPro, and a pipeline combining homology modelling with rigid-body docking informed by ML-based epitope and paratope prediction (AbAdapt). We find that AlphaFold-Multimer outperformed other methods, although the absolute performance leaves considerable room for improvement. AlphaFold-Multimer models of lower-quality display significant structural biases at the level of tertiary motifs (TERMs) towards having fewer structural matches in non-antibody containing structures from the PDB. Specifically, better models exhibit more common PDB-like TERMs at the antibody-antigen interface than worse ones. Importantly, the clear relationship between performance and the commonness of interfacial TERMs suggests that scarcity of interfacial geometry data in the structural database may currently limit application of machine learning to the prediction of antibody-antigen interactions.

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Recent updates on correlates of vaccine-induced protection

Abstract: Correlates of protection are key for vaccine development against any pathogen. In this paper we summarize recent information about correlates for vaccines against dengue, Ebola, influenza, pneumococcal, respiratory syncytial virus, rotavirus, shigella, tuberculosis and Zika virus.

Cited by 25 publications

References 71 publications

Serological assessment of the durability of vaccine-mediated protection against SARS-CoV-2 infection

Serological assessment of the durability of vaccine-mediated protection against SARS-CoV-2 infection

Towards establishing correlates of protection against shigellosis: assessing immunological endpoints across immune responses to the Shigella sonnei Generalized Modules for Membrane Antigens (GMMA) candidate vaccine (1790GAHB).

A Comparison of Antibody-Antigen Complex Sequence-to-Structure Prediction Methods and their Systematic Biases

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