RSV vaccine research contends with a post-Covid landscape
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RSV vaccines improve on technology but contend with a post-Covid world

By Manasi Vaidya 24 Sep 2021 (Last Updated September 24th, 2021 09:57)

Post-Covid changes including social distancing measures and seasonal shifts have challenged RSV vaccine development projects.

RSV vaccines improve on technology but contend with a post-Covid world
RSV is the most common cause of respiratory hospitalisation in infants. Credit: Getty Images

Need to Know

  • A recent unseasonal rise in infections has reduced clarity on upcoming RSV season dates
  • Several ongoing trials may find it difficult to prove the benefit of vaccines if there are fewer RSV infections
  • Newer vaccines have an improved vaccine design focused on the RSV prefusion F protein

While the Covid-19 pandemic brought vaccine research to the fore, it upended clinical research in several therapy areas like respiratory syncytial virus (RSV), slowing it down considerably last year. With the field now developing several RSV vaccines, these candidates will have to deal with evolving RSV season dynamics as they enter the development race.

Clinical studies had to contend with tougher recruitment challenges due to Covid-19-related restrictions and upcoming trials will also have to work with evolving social distancing measures due to the emerging SARS-CoV-2 variants. In such an environment, conducting a study that will record enough RSV infections to show a vaccine’s activity against a placebo could also be difficult, experts said.

Typically, the RSV season is thought to start in October and peak from late December to mid-February in the US; but this has now shifted to a later date. The recent spike in RSV cases, which are typically not observed in the summer, as noted by the CDC, has changed the RSV research landscape significantly.

Still, in terms of currently investigational RSV vaccines, those by Pfizer, GlaxoSmithKline, Moderna and Janssen have been designed to target the virus’ prefusion F protein which several failed vaccines in the past did not. This gives them a leg up when it comes to effectively inducing a relevant level of immunogenicity. However, each company uses a different technology with no clear winner yet.

While Pfizer started its Phase III vaccine trial for participants who are 60 years and older earlier this month, Moderna plans to begin a similar one with its mRNA-1345 vaccine by the end of this year. GSK and Janssen on the other hand already initiated their Phase III programs for older adults, and GSK expects interim results in the second half of 2022.

Both GSK and Pfizer are also exploring these vaccines for maternal immunisation.

Moderna and GSK did not respond to a request for comment, while Janssen did not comment before deadline. A Pfizer spokesperson pointed this news service to its RSV vaccine data described in its Q2 results and other publicly available information.

RSV vaccine research: trial enrolment challenges

The Covid-19 pandemic has dramatically changed the epidemiology of RSV, said Seattle Children’s Hospital paediatric infectious diseases professor Dr Janet Englund. Indeed, the RSV season in 2020 was very short or absent in many places with few cases, experts said. While several vaccination guidelines for Covid-19 and RSV were being mapped out, trial recruitment had essentially stopped, said Dr Renato Stein, a paediatrician at the Pontifical Catholic University of Rio Grande do Sul.

Stein and Englund, both of whom are closely involved in RSV research, said conducting trials can be challenging in such circumstances. Unless some RSV infections are reported in trial participants, there won’t be a chance to record a positive outcome in reducing infections or hospitalisations, Stein explained. Trial design projections have traditionally been based on typical RSV infection and hospitalisation rate, said NYU Long Island School of Medicine paediatric infectious disease chief Dr Leonard Krilov. But because of Covid-19 and reduced RSV disease seen in the last year, even the clinical protection data with investigational vaccines can be skewed, he said. However, NIAID Vaccine Research Center deputy director Dr Barney Graham said if a vaccine is only effective at peak immunity then it is not very compelling.

Given the rise of Covid-19 infections, social distancing and daycare closures would be implemented in certain parts of the world. Whether that will decrease RSV cases in the coming days, or the traditional seasonality of infections will return to what was seen prior to the pandemic, is not clear, Krilov said. Studies may now take a year or two longer than originally planned, he added. However, not all studies are being done in younger infants and those for older adults won’t be affected by centres closed for younger children, said Ohio State University College of Medicine RSV biologist Mark Peeples.

Generally though, Covid-19 may make it difficult to recruit participants if they are required to go to a trial centre, Peeples added. Moreover, many researchers who typically run these trials have also been primarily engaged in Covid-19 vaccine studies, so resources may be relatively limited, Englund pointed out.

Another factor that complicates trial protocols is the unusual surge in cases being reported at this time of year, said Peeples. As per Centers for Disease Control and Prevention (CDC) data, 2071 cases of RSV infections were reported in the week of 18 September this year compared to 273 around the same time in 2019, as per PCR testing. Trials may have been planned while considering a certain number of RSV infections seen in 2019, but the number expected in 2022 will now have to consider the current surge in the summer, Stein said. Conducting a study may be more complicated, but the changed RSV season should not affect a trial’s chances of success, Graham said.

Improved vaccine design bolsters expectations

The research field now has a better understanding of the protective component and role of the prefusion F protein in eliciting an immune response, Krilov said. In fact, Graham said the identification of the prefusion F protein helped pave the way for the identification of the spike protein for developing Covid-19 vaccines.

Moderna’s candidate is an mRNA-based vaccine while Pfizer is studying a bivalent protein-based vaccine. Janssen is studying a recombinant viral vector vaccine, the same technology used in its authorised Covid-19 vaccine. GSK’s maternal RSV vaccine contains a recombinant subunit prefusion RSV antigen, while its vaccine for older adults is based on the same design but combined with a proprietary adjuvant. While the mutations they target, or adjuvants used in these vaccines may be different they are relying on the same basic biology, Graham said. To illustrate how RSV vaccines have advanced, Graham said that while earlier the most promising candidates elicited only 2–3 fold antibody titers , the current vaccines can induce 12–14 fold antibody titers.