Prevalent levels of RSV serum neutralizing antibodies in healthy adults outside the RSV-season

Abstract

One of the main challenges in early clinical research with respiratory syncytial virus (RSV) live-attenuated vaccines (LAVs) is to assess immunogenicity in healthy adults. Healthy adults will have preexisting levels of serum neutralizing antibodies that could prematurely neutralize the LAV and underestimate the potential effect of the vaccine on the immune system. Data on prevalence and distribution of virus neutralizing titers (VNTs) in healthy adults is limited and there is no absolute threshold for protection against RSV-infection that can serve as an eligibility criterion in early phase trials. We assessed the RSV-specific serum VNT in healthy adults outside the Dutch RSV-Season in two clinical studies performed in 2017 (exploratory study, n = 100) and 2018 (first-in-human LAV-study, n = 190) using the same neutralizing assay. Our findings show that the prevalence and distribution of serum VNT was overall consistent in the two clinical studies. Log 2 VNTs were normally distributed, distributions of VNTs were similar and there was no statistical difference in mean log 2 VNT for both studies ( p = .3). Serum VNTs were comparable during the 6 months of screening in the FIH LAV-study. Our findings will help to determine a cutoff serum VNT to be used as an eligibility criterion in future early phase clinical trials.

Seroprevalence of neutralizing antibodies against the respiratory syncytial virus in healthy adults in Guangzhou, southern China

“…A recent report revealed the seroprevalence of anti-RSV NAbs in healthy adults in the Netherland was 100% outside RSV season in 2017. 12 Here the overall proportion of anti-RSV NAbsseropositive healthy adults (titers > 18) in Guangzhou was 85%, lower than that in the Netherland, which may be because the positive judgment was prevented CPEs not less than 50% instead of completely prevented. The seropositive rate of anti-RSV NAbs in Guangzhou was similar to that in the Netherland, indicating anti-RSV NAbs may commonly present in healthy adults in Asia and Europe even all over the world.…”

“…Most seroprevalence studies of RSV have focused on the pediatric population since RSV‐associated ALRI is a major cause of pediatric mortality worldwide. A recent report revealed the seroprevalence of anti‐RSV NAbs in healthy adults in the Netherland was 100% outside RSV season in 2017 12 . Here the overall proportion of anti‐RSV NAbs‐seropositive healthy adults (titers > 18) in Guangzhou was 85%, lower than that in the Netherland, which may be because the positive judgment was prevented CPEs not less than 50% instead of completely prevented.…”

“…Seroepidemiological studies on NAbs against RSV would be helpful for gaining some detailed knowledge of the humoral immune response to RSV. To our knowledge, only one publication reported the prevalence and distribution of the RSV‐specific serum virus neutralizing titers in the healthy adult population 12 . There is currently insufficient data available on the seroprevalence and distribution of anti‐RSV NAbs in the healthy adult population.…”

“…To our knowledge, only one publication reported the prevalence and distribution of the RSV-specific serum virus neutralizing titers in the healthy adult population. 12 There is currently insufficient data available on the seroprevalence and distribution of anti-RSV NAbs in the healthy adult population.…”

Respiratory Syncytial Virus

“…35 39 40 One study shows that up to 54% of healthy adult volunteers have viral neutralizing titers below threshold when checked outside of the usual RSV season. 41…”