Designing the Next Generation of Vaccines: Relevance for Future Pandemics

Domínguez‐Andrés, Jorge; Crevel, Reinout van; Divangahi, Maziar; Netea, Mihai G.

doi:10.1128/mbio.02616-20

Cited by 24 publications

(17 citation statements)

References 100 publications

(116 reference statements)

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“…Fourth, Dr. Netea proposed a strategy to design next-generation vaccines termed "amplified" vaccines, which would contain classical vaccine components and metabolic/epigenetic modulators with the capacity to amplify the function of immunity. 144 Such approaches might not only improve the nonspecific trained immunity against different types of pathogens but also potentially enhance the antigen-specific adaptive immune responses, as we indicated in previous sections. The potential of this novel vaccine strategy is waiting to be tested in the coming years.…”

Section: Discussionmentioning

confidence: 90%

“…Third, the question remains to be answered whether short‐term induction/inhibition of molecules that mediate trained immunity is sufficient to write or remove the associated epigenetic markers and programming of trained immunity, or only provides dynamic interference? Fourth, Dr. Netea proposed a strategy to design next‐generation vaccines termed “amplified” vaccines, which would contain classical vaccine components and metabolic/epigenetic modulators with the capacity to amplify the function of immunity 144 . Such approaches might not only improve the nonspecific trained immunity against different types of pathogens but also potentially enhance the antigen‐specific adaptive immune responses, as we indicated in previous sections.…”

Section: Discussionmentioning

confidence: 99%

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Trained immunity: A Yin‐Yang balance

Lowrie

et al. 2022

MedComm

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Traditionally, immune memory is regarded as an exclusive hallmark of adaptive immunity. However, a growing body of evidence suggesting that innate immune cells show adaptive characteristics has challenged this dogma. In the past decade, trained immunity, a de facto innate immune memory, has been defined as a long‐term functional reprogramming of cells of the innate immune system: the reprogramming is evoked by endogenous or exogenous insults, the cells return to a nonactivated state and subsequently show altered inflammatory responses against a second challenge. Trained immunity became regarded as a mechanism selected in evolution to protect against infection; however, a maladaptive effect might result in hyperinflammation. This dual effect is consistent with the Yin‐Yang theory in traditional Chinese philosophy, in which Yang represents active, positive, and aggressive factors, whereas Yin represents passive, negative, and inhibitory factors. In this review, we give a brief overview of history and latest progress about trained immunity, including experimental models, inductors, molecular mechanisms, clinical application and so on. Moreover, this is the first time to put forward the theory of Yin‐Yang balance to understand trained immunity. We envision that more efforts will be focused on developing novel immunotherapies targeting trained immunity in the coming years.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Trained immunity: A Yin‐Yang balance

Lowrie

et al. 2022

MedComm

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“…Which vaccines/adjuvants can induce trained immunity, and how, is currently one of the hottest topics in the field (Box 3). A better understanding of the mechanisms may make it possible in the future, to precisely target the trained immunity metabolic or epigenetic pathways, with pharmacological modulators, to program and tailor immune training, as recently discussed (81). The genetic depletion and pharmacological inhibition of SHIP-1 was shown for instance to improve the b-glucan mediated training of macrophages (82).…”

Section: Trained Immunity-based Vaccines Trained Immunity-inducing Vamentioning

confidence: 96%

Optimize Prime/Boost Vaccine Strategies: Trained Immunity as a New Player in the Game

et al. 2021

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Most vaccines require multiple doses to induce long-lasting protective immunity in a high frequency of vaccines, and to ensure strong both individual and herd immunity. Repetitive immunogenic stimulations not only increase the intensity and durability of adaptive immunity, but also influence its quality. Several vaccine parameters are known to influence adaptive immune responses, including notably the number of immunizations, the delay between them, and the delivery sequence of different recombinant vaccine vectors. Furthermore, the initial effector innate immune response is key to activate and modulate B and T cell responses. Optimization of homologous and heterologous prime/boost vaccination strategies requires a thorough understanding of how vaccination history affects memory B and T cell characteristics. This requires deeper knowledge of how innate cells respond to multiple vaccine encounters. Here, we review how innate cells, more particularly those of the myeloid lineage, sense and respond differently to a 1st and a 2nd vaccine dose, both in an extrinsic and intrinsic manner. On one hand, the presence of primary specific antibodies and memory T cells, whose critical properties change with time after priming, provides a distinct environment for innate cells at the time of re-vaccination. On the other hand, innate cells themselves can exert enhanced intrinsic antimicrobial functions, long after initial stimulation, which is referred to as trained immunity. We discuss the potential of trained innate cells to be game-changers in prime/boost vaccine strategies. Their increased functionality in antigen uptake, antigen presentation, migration, and as cytokine producers, could indeed improve the restimulation of primary memory B and T cells and their differentiation into potent secondary memory cells in response to the boost. A better understanding of trained immunity mechanisms will be highly valuable for harnessing the full potential of trained innate cells, to optimize immunization strategies.

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“…The development of vaccines is one of the most important medical interventions in infectious disease prevention. 3 Generating protective T cell and B cell immune responses is a critical element of vaccine development. 4 SARS-CoV-2 is a singlestranded RNA virus that replicates in the cytoplasm and consists of four structural proteins: spike (S) protein, envelope (E) protein, membrane (M) protein, and nucleocapsid (N) protein.…”

Section: What Is the Key Immunogen For Covid-19 Vaccines?mentioning

confidence: 99%

A review of leading COVID-19 vaccines, the quest for immune protection, and its key challenges. Part 3: Covid-19 vaccines – Key challenges and translational science

Hartshorne¹,

Villiers²

2021

Preprint

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Rationale• Developing and deploying safe and effective COVID-19 vaccines are faced with many challenges and unanswered questions.• Massive amounts of heterogenic scientific data are being generated that are needed rapidly to advance vaccine development, protect people and restore normality. • The purpose of Part 3 of this four-part series is to review the scientific considerations related to key challenges associated with COVID-19 vaccines and immune protection with the focus of making this data more meaningful and open for clinicians.Key points• The primary immunogen (antigen) required to induce neutralising antibodies (humoral) and T cell (cellular) immune responses is the S-protein fragment of SARS-CoV-2. • Currently, the evidence is firmly pointing towards neutralising antibodies, being more critical for protection.• Long-term protective or durable immune memory is driven by virus-specific T cell and B cell responses (adaptive immunity).• Circulating antibody titres are not predictive of T cell immune memory.• Durable immune memory is a crucial factor to sustain herd immunity.• Adjuvants are added to certain vaccines to provoke a more robust and durable immune response.• Adjuvants that provoke TH1-biased immune responses are preferred. • 90% of adults are seropositive for 'common cold' CoV strains.• There is a cross-reactivity between specific T cell of SARS-CoV-2 and 'common cold' CoV's.• Prior infection with 'common cold' can play a potentially protective role.• Seropositive individuals present with a rapid and higher antibody immune response after a single dose with an mRNA vaccine.• Vaccine-induced immune responses resulting in non-neutralising antibodies, low antibody titres, and abnormal T cell responses (TH2- biased) are potential risks for serious enhanced disease events but unlikely events.• Vaccine strategies aimed at inducing high titres on neutralising antibodies and TH1- biased immune responses reduce the risk of serious adverse events.• Emerging variants of concern are extremely infectious, highly transmissible and threatens the protective efficacy of current vaccines.Public health implications• A rapid global vaccination campaign combined with standard mitigation measures to stop transmission is the best defence against the emergence of further SARS-CoV-2 variants and the safest way to attain herd immunity.• Booster immunisations may be required to promote or improve the durability and strength of vaccine immunity.

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Designing the Next Generation of Vaccines: Relevance for Future Pandemics

Cited by 24 publications

References 100 publications

Trained immunity: A Yin‐Yang balance

Trained immunity: A Yin‐Yang balance

Optimize Prime/Boost Vaccine Strategies: Trained Immunity as a New Player in the Game

A review of leading COVID-19 vaccines, the quest for immune protection, and its key challenges. Part 3: Covid-19 vaccines – Key challenges and translational science

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