COVID-19 vaccination: The road ahead Altmann, Daniel M; Boyton, Rosemary J
Science (American Association for the Advancement of Science),
03/2022, Volume:
375, Issue:
6585
Journal Article
Peer reviewed
A diverse array of successful, first-generation SARS-CoV-2 vaccines have played a huge role in efforts to bring the COVID-19 pandemic under control, even though inequitable distribution still leaves ...many vulnerable. Additional challenges loom for the next phase. These include optimizing the immunological rationale for boosting-how often and with what-and the best approaches for building a future-proofed, durable immune repertoire to protect against oncoming viral variants, including in children. The landscape of vaccine producers and technologies is likely to become even more heterogeneous. There is a need now for appraisal of future approaches: While some favor frequent boosting with the first-generation, ancestral spike vaccines, others propose frequent readjustment using current variant sequences, polyvalent vaccines, or pan-coronavirus strategies.
The route to certainty on the degree and nature of the immunity required for protection will require evidence from formal proofs using approaches such as titrated transfers of antibodies and T ...lymphocytes to define protection in non-human primate models, as used, for example, in studies of Ebola virus.9 A study of survivors of SARS showed that about 90% had functional, virus-neutralising antibodies and around 50% had strong T-lymphocyte responses.10 These observations bolster confidence in a simple view that most survivors of severe COVID-19 would be expected to have protective antibodies. There are more than 100 candidate COVID-19 vaccines in development, with a handful in, or soon to be in, phase 1 trials to assess safety and immunogenicity.4 Candidate vaccines encompass diverse platforms that differ in the potency with which immunity is stimulated, the specific arsenal of immune mediators mobilised, the number of required boosts, durability of protection, and tractability of production and supply chains.3,4 Safety evaluation of candidate COVID-19 vaccines will need to be of the highest rigour. Some features of the immune response induced by infection, such as high concentrations of tumour necrosis factor and interleukin 6, which could be elicited by some candidate vaccines, have been identified as biomarkers of severe outcome.19 Researchers should be commended for decades of iterative efforts, bringing us to a point where there are many candidate vaccines in development against a novel virus first sequenced in January, 2020.
An important challenge during the COVID-19 pandemic has been to understand asymptomatic disease and the extent to which this may be a source of transmission. As asymptomatic disease is by definition ...hard to screen for, there is a lack of clarity about this aspect of the COVID-19 spectrum. Studies have considered whether the prevalence of asymptomatic disease is determined by differences in age, demographics, viral load, duration of shedding, and magnitude or durability of immunity. It is clear that adaptive immunity is strongly activated during asymptomatic infection, but some features of the T cell and antibody response may differ from those in symptomatic disease. Areas that need greater clarity include the extent to which asymptomatic disease leads to persistent symptoms (long COVID), and the quality, quantity and durability of immune priming required to confer subsequent protection.
Immunity to SARS-CoV-2 variants of concern Altmann, Daniel M; Boyton, Rosemary J; Beale, Rupert
Science (American Association for the Advancement of Science),
03/2021, Volume:
371, Issue:
6534
Journal Article
Summary
The field of cancer immunology stepped into the limelight this year when James P. Allison and Tasuku Honjo received the Nobel Prize in Physiology or Medicine for their discovery of cancer ...therapy by inhibition of negative immune regulation. Among many exciting advances contributing to the coming of age of tumour immunology as a viable clinical specialty has been the ability to progress from the initial elucidation of tumour antigens, such as the melanoma antigen, MAGE‐1, to high‐throughput sequencing facilitating identification of T cell epitopes from diverse tumour neoantigens. This has resulted from the convergence of expertise in tumour biology, next‐generation sequencing, T cell and structural immunology, and predictive algorithms. Among many examples, immunotherapy for ovarian cancer has been one of the beneficiaries of these advances, leading to a number of recent and ongoing clinical trials.
Rapid vaccine-induced population immunity is a key global strategy to control COVID-19. Vaccination programmes must maximise early impact, particularly with accelerated spread of new variants.1 Most ...vaccine platforms use a two-dose prime-boost approach to generate an immune response against the virus S1 spike protein, the titres of which correlate with functional virus neutralisation and increase with boosting.2,3 To enable larger numbers of people to receive the first dose, delayed administration of the second dose has been advocated and implemented by some.1 The impact of previous SARS-CoV-2 infection on the need for boosting is not known. To test this, we undertook a nested case-control analysis of 51 participants of COVIDsortium,4,5 an ongoing longitudinal observational study of health-care workers (HCWs) in London who underwent weekly PCR and quantitative serology testing from the day of the first UK lockdown on March 23, 2020, and for 16 weeks onwards. 24 of 51 HCWs had a previous laboratory-confirmed mild or asymptomatic SARS-CoV-2 infection, as confirmed by positive detection of antibodies against the SARS-CoV-2 nucleocapsid (Elecsys Anti-SARS-CoV-2 N ECLIA, Roche Diagnostics, Burgess Hill, UK) or the receptor binding domain of the SARS-CoV-2 S1 subunit of the spike protein (anti-S; Elecsys anti-SARS-CoV-2 spike ECLIA, Roche Diagnostics), whereas 27 HCWs remained seronegative.
As SARS-CoV-2 vaccines are deployed worldwide, a comparative evaluation is important to underpin decision-making. We here report a systematic literature review and meta-analysis of Phase I/II/III ...human trials and non-human primates (NHP) studies, comparing reactogenicity, immunogenicity and efficacy across different vaccine platforms for comparative evaluation (updated to March 22, 2021). Twenty-three NHP and 32 human studies are included. Vaccines result in mostly mild, self-limiting adverse events. Highest spike neutralizing antibody (nAb) responses are identified for the mRNA-1273-SARS-CoV and adjuvanted NVX-CoV2373-SARS-CoV-2 vaccines. ChAdOx-SARS-CoV-2 produces the highest T cell ELISpot responses. Pre-existing nAb against vaccine viral vector are identified following AdH-5-SARS-CoV-2 vaccination, halving immunogenicity. The mRNA vaccines depend on boosting to achieve optimal immunogenicity especially in the elderly. BNT162b2, and mRNA-1273 achieve >94%, rAd26/5 > 91% and ChAdOx-SARS-CoV-2 > 66.7% efficacy. Across different vaccine platforms there are trade-offs between antibody binding, functional nAb titers, T cell frequency, reactogenicity and efficacy. Emergence of variants makes rapid mass rollout of high efficacy vaccines essential to reduce any selective advantage.
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