Nature Milestones in Vaccines

Bringing truly personalized cancer vaccination with tumour neoantigens to the clinic will require overcoming the challenges of optimized vaccine design, manufacturing and affordability, and identification of the most suitable clinical setting.

Rebecca Chandler from the Uppsala Monitoring Centre discusses how the COVID-19 pandemic could be the catalyst that propels vaccine safety surveillance into the twenty-first century.

Here, Peter Hotez and colleagues discuss the advantages of using an aluminium-based adjuvant in candidate COVID-19 vaccines.

New approaches to vaccine development have generated exciting results over the past 18 months. Focusing on respiratory syncytial virus infection, influenza and tuberculosis, Fauci and Mascola discuss the impact of structure-based vaccine design, gene-based vaccine platforms and advances in adjuvant development.

Insights into the interactions between pro- and anti-vaccination clusters on Facebook can enable policies and approaches that attempt to interrupt the shift to anti-vaccination views and persuade undecided individuals to adopt a pro-vaccination stance.

An overview of the effects of vaccines on global morbidity and mortality, vaccine safety issues, and the hurdles involved in proceeding from vaccine discovery to successful implementation.

This Review, aimed at a broad scientific audience, provides an introductory guide to the history, development and immunological basis of vaccines, immunization and related issues to provide insight into the challenges facing immunologists who are designing the next generation of vaccines.

Pulendran and colleagues use a systems biology analysis to reveal distinct transcriptional signatures of antibody responses to different classes of human vaccines.

Vaccination offers protection against infectious diseases, yet pre-existing criteria that predict vaccine efficacy or adverse events remain unknown. Hayday and colleagues identify cellular and molecular signatures in humans immunized with adjuvanted swine flu vaccine.

Identifying molecular predictors of effective vaccination is an important clinical and technical goal. Pulendran and colleagues use a systems biology approach to study human responses to vaccination against influenza and determine the correlates of immunogenicity.

Cancer vaccines that self-assemble into uniform nanoparticles improve tumor clearance.

Petsch et al. apply mRNA vaccination for the first time to infectious disease, demonstrating immunogenicity and/or protective effects against influenza virus in mice, ferrets and pigs.

The highly conserved influenza virus hemagglutinin (HA) stalk represents a potential target for a broadly protective vaccine. Here, the authors show that immunization with nucleoside-modified mRNA encoding full-length HA formulated in lipid nanoparticles elicits HA stalk-specific antibodies and protects from heterosubtypic virus infection.

A dual positron emission tomography–near-infrared probe enables the visualization of the early trafficking dynamics of an injected model mRNA vaccine in non-human primates.

A macroporous material encapsulating an immune-cell-activating cytokine, an adjuvant and tumour-associated antigens elicits prophylactic immunity to acute myeloid leukaemia in mice, and eradicates the disease when combined with chemotherapy.

Tuning the pharmacokinetics of peptide-based antitumour vaccines by fusing the peptide epitopes to protein carriers optimizes the immunogenicity of the vaccines in mice.

In a dose-escalation study of the COVID-19 RNA vaccine BNT162b1 in 45 healthy adults, RBD-binding IgG concentrations and SARS-CoV-2 neutralizing titres in sera increased with dose level and after a second vaccine dose.

A vaccine preventing infection and transmission of SARS-CoV-2 is needed. Here, Wu et al. generate an adenovirus-vector vaccine expressing SARS-CoV-2 spike protein and show that a single dose of mucosal vaccination protects mice and ferrets from infection and inhibits virus replication in the upper respiratory tract.

Here, the authors develop a self-amplifying RNA encoding the SARS-CoV-2 spike protein encapsulated within a lipid nanoparticle as a vaccine candidate and show induction of neutralization antibody titers in mice that are comparable to titers in convalescent sera of patients.

There is currently no licensed SARS-CoV-2 vaccine. Here, the authors generate an optimized DNA vaccine candidate encoding the SARS-CoV-2 spike antigen, demonstrating induction of specific T cells and neutralizing antibody responses in mice and guinea pigs. These initial results support further development of this vaccine candidate.

Neonates represent a challenging group for vaccination. Effective vaccine programs will need to take into account a number of factors including gender and non-specific vaccine effects.

With record levels of vaccine hesitancy and one of the most drastic reinforcements of vaccine mandates in recent years, there is much to learn from the French experience.

Recent findings in the SIV-monkey model provide new evidence that stimulating effective CD8⁺ T cell immunity could provide protection. McMichael and Koff explore the path forward for optimizing such responses in humans.

Emerging viral diseases present a huge and increasingly important global threat to public health systems. Graham and Sullivan discuss the challenges presented by emerging viral diseases and discuss how innovations in technology and policy can address this threat.

Technological advances in antigen discovery, genomics and immunological monitoring offer tremendous potential for revolutionizing vaccine development. On 5–6 February 2014, 35 leading vaccine scientists met to consider how best to harness these advances and spur innovation.

Companies are doing their best to accelerate experimental drugs and vaccines for COVID-19 through the pipeline. Each faces its own set of challenges, but all agree on the need for a radical rethink of the clinical development process for pandemics.

In responding to future influenza pandemics and other infectious agents, plasmid DNA overcomes many of the limitations of conventional vaccine production approaches.

Potent dendritic-cell cancer vaccines could be used to induce functional antitumour immunity without off-target toxicity.

This Review outlines the guiding immunological principles for the design of coronavirus disease 2019 (COVID-19) vaccine strategies and analyses the current COVID-19 vaccine landscape and the challenges ahead.

In this Viewpoint article, members of the Optimmunize consortium discuss the evidence for non-specific and sex-differential effects of vaccines and how this information might inform vaccine design and policy, including in relation to the COVID-19 pandemic.

Vaccine trials against Mycobacterium tuberculosis (Mtb) are showing encouraging results. This Review discusses current Mtb vaccine design in the light of new insights into the immunology of tuberculosis infection.

Developing universal influenza virus vaccines will require understanding how broad and long-lived antibody responses to natural infection with influenza A virus are generated, a topic that has benefited greatly from technologies that enable the analysis of single human B cells.

Here, Hotez and colleagues highlight the two ‘faces’ of immune enhancement that could impact COVID-19 vaccine design.

Could the BCG vaccine be used to bridge the gap until a specific COVID-19 vaccine is developed? Luke O’Neill and Mihai Netea discuss the science behind this approach.

The generation of an HIV vaccine remains the holy grail for eliminating HIV infection worldwide. Major advances in 2018 centred on sequential multi-immunogen strategies that are designed to induce broadly neutralizing antibodies, identifying new targets and defining new approaches to immunogen evaluation.

Dendritic cell vaccines have been widely investigated as a type of cancer immunotherapy, but their promise has not yet been realized. Kandalaft and colleagues propose that a prime and boost approach — primed with either standard therapies or dendritic cell vaccines and boosted with a personalized synthetic vaccine — could help fulfil the potential of such vaccines. They discuss improvements in dendritic cell vaccines that have enabled prime–boost approaches, as well as challenges for adoption.

Current seasonal influenza vaccines lack efficacy against drifted or pandemic virus strains, and the development of novel vaccines that elicit broader immunity represents a public health priority. Here, Nabel and colleagues discuss approaches to improve vaccine efficacy which harness new insights from influenza antigen structure and human immunity, highlighting major targets, vaccines in development and ongoing challenges.

To efficiently prevent cancers associated with human papillomavirus (HPV) infection, especially cervical cancer, effective vaccines and high vaccination coverage are required. This Review provides insight into virological, immunological and strategical progress in HPV vaccines as well as implementation and potential advances.

The recent epidemic of Zika virus (ZIKV) in the Americas has revealed the devastating consequences of ZIKV infection, particularly in pregnant women. In this Progress article, Barouch and colleagues discuss recent preclinical studies and lessons learned from first-in-human clinical trials with ZIKV vaccines.