Completed Infection & Immunity Lungs & Breathing

Induction of protective mucosal RSV F-specific immunity by a novel intranasal vaccine .

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AI plain-English summary

A nasal spray vaccine aims to train the immune system to block respiratory syncytial virus (RSV) before it can take hold. RSV causes severe lung infections in infants and older adults, yet no effective vaccine exists. The problem is that natural RSV infection leaves the body with weak and short-lived immune memory, especially the nasal antibodies that are the first line of defence. This vaccine, called SynGEM, delivers a stabilised form of the key RSV F protein attached to a bacterium-like particle that acts as a stimulant. In animal studies, it generates strong, lasting antibody responses in both the nose and the bloodstream. The researchers will test SynGEM in human volunteers using a controlled infection model to see whether it produces durable protection and to confirm that nasal IgA antibodies are a reliable marker of immunity. If successful, this approach could lead to a practical, needle-free vaccine that prevents RSV infection at the point of entry, reducing hospitalisations and the burden on healthcare systems during winter respiratory seasons.

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Despite the urgent global need, there is currently no effective vaccine against respiratory syncytial virus (RSV). Our recent experimental human RSV infection studies show that nasal IgA against the major conserved RSV glycoprotein F is the best available correlate of protection against infection and that impaired IgA memory may explain the transience of protection after RSV infection. These new data suggest that an optimal vaccine strategy is to use nasal vaccination to generate specific local and systemic antibody, circumventing the defect in B cell memory that follows natural infection. SynGEM is an innovative intranasal vaccine against RSV that induces potent protective B cell immunity in animal models; it contains an optimised form of the F glycoprotein linked to an immunostimulatory bacterium-like particle (BLP) carrier. In phase I trials of a related intranasal influenza vaccine, BLPs were safe and highly effective at inducing local and systemic antiviral responses. The human vo lunteer RSV challenge model studies at Imperial College provides an excellent opportunity to evaluate the capacity of SynGEM to induce long-lasting protective local and systemic RSV-specific immunity in humans, rapidly advancing the development of this innovative vaccine approach and validating mucosal IgA as a true correlate of protection against RSV.

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Researchers

Kees Leenhouts (EPMC Awardee)

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