The recent rise of the "tripledemic" – the concurrent spread of the influenza virus, SARS-CoV-2 virus, and respiratory syncytial virus (RSV) – is posing significant risks, especially to older adults and those with chronic conditions or compromised immune systems.[1] Although flu and RSV have shown strong seasonal patterns, peaking in the winter months, the convergence of these viruses with COVID-19 exacerbates healthcare pressures during the winter, adding significant strain to hospital resources. The overlap in symptoms of these viruses – including fever, cough, runny or stuffy nose, and sore throat – makes it difficult for healthcare professionals to identify the specific virus from symptoms alone with distinguishing diagnostic tests required to facilitate exact diagnosis and inform treatment strategies.
The availability of Human Challenge Trials (HCT) represents a significant leap forward in our list of tools to help tackle these diseases. This blog explores how such trials can fast-track the development of multivalent vaccines, designed to protect against multiple viruses at the same time. The need for such vaccines has never been more urgent.
Currently, vaccines for flu, RSV and COVID-19 are formulated independently and administered separately. The tripledemic poses a unique challenge, and so a combination vaccine, which can protect against all three or even multiple viruses, is an ideal solution. Multivalent vaccines offer several benefits:
Developing these vaccines through traditional methods, however, is time-consuming and complicated in terms of regulatory approval and formulation to ensure each vaccine component still remains effective and safe once combined. Regulators typically require evidence of at least safety and immunogenicity of the combined vaccine, and potentially also efficacy, even if these parameters have been established for the individual vaccines.
Human challenge trials (HCT), sometimes also referred to as Controlled Human Infection Studies, streamline this process by allowing simultaneous testing of multiple antigens and play a crucial role in vaccine development, especially for new technologies like mRNA vaccines. Unlike traditional field trials, which rely on participants naturally encountering a virus, HCT take a more controlled approach – experimentally inoculating the trial subjects with a specific medical grade version of the virus (the challenge virus). Separately inoculating difference participants on the trial with a different target virus ensure efficacy data is collected against all pathogen targets and facilitates efficient multivalent vaccine development.
Advantages of HCT include:
HCT can also be used to complement field studies by supplying additional data for a specific pathogen in a combination vaccine that was in low circulation during the field trial, so the efficacy data is effectively supplemented by HCT data.
Whilst HCT are often run in healthy adults with no risk factors for severe illness such that they are expected to clear the infection without invention by their own immune response, HCT can also be against pathogens where an individual’s existing immunity is not expected to be sufficient to clear an infection. In such incidences, proven treatments would need to be available. Malaria is an example of this as the strain of the parasite can be carefully controlled and chosen for a HCT, to ensure that it is sensitive to antimalarial drugs and not resistant so that we can treat the subject in the HCT to prevent the development of malarial disease symptoms.
Human challenge trials are revolutionising the approach to vaccine development by offering a faster, more precise, and efficient approach to studying vaccine efficacy. As the global leader in Human Challenge Trials, in 2021, hVIVO performed the World’s first COVID-19 HCT, set up during the height of the pandemic to provide a tool to quickly test a range of different vaccines to ascertain the best one to use should the first generation of vaccines had not proven to be successful. This model has now progressed with the development of later variants of the SARS-CoV-2 virus, such as Omicron BA 5.
Another groundbreaking example is studies at hVIVO that have provided efficacy data, which had a massively positive impact in bringing RSV vaccines to market in the last few years despite there being no vaccine available since RSV was isolated in 1956. Every year in the US, the CDC estimates RSV causes 60,000 to 80,000 hospitalisations and 100–300 deaths in children under 5 years and up to 160 000 hospitalisations and 6000–10,000 deaths in adults over 65 years.[2] HCT, conducted at hVIVO, first demonstrated the efficacy of a novel RSV vaccine, which gave confidence to the market that RSV vaccination may be possible. This led to several pharmaceutical companies expediting their RSV vaccine programmes by testing their efficacy in a HCT at hVIVO and obtaining fast-track and breakthrough status with the regulators, which facilitated subsequent clinical development steps. Consequently, the quality data from the HCT gave both the vaccine producers and the regulators confidence that the vaccine can work and provide an effective solution for this unmet medical need.[3]
With RSV vaccines now on the market, thanks to human challenge trials conducted at hVIVO, there is greater potential to address the challenges posed by the tripledemic, by integrating such studies to significantly shorten the timeline in developing and bringing multivalent vaccines to market. While this remains a long-term objective, the development of combination vaccines, through such trials underline its ethical and practical value. Not only will this be a cornerstone to managing several respiratory viruses at the same time, but also has the potential to save thousands of lives and alleviate the burden on worldwide healthcare systems, particularly if the higher vaccine update expectations of a combination vaccine are realised.
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