Safety and immunogenicity following co-administration of Yellow fever vaccine with Tick-borne encephalitis or Japanese encephalitis vaccines: Results from an open label, non-randomized clinical trial
Authors: Sandberg John Tyler , Löfling Marie , Varnaitė Renata , Emgård Johanna , Al-Tawil Nabil , Lindquist Lars , Gredmark-Russ Sara , Klingström Jonas , Loré Karin , Blom Kim , Ljunggren Hans-Gustaf 
Published: July 2022

AbstractBackgroundFlavivirus infections pose a significant global health burden underscoring the need for the development of safe and efficient vaccination strategies. Available flavivirus vaccines are from time to time concomitantly delivered to individuals in need. Co-administration of different vaccines saves time and visits to health care units and vaccine clinics. It serves to provide protection against multiple pathogens in a shorter time-span, both for individuals living in, or travelling to, endemic areas. However, safety and immunogenicity-related responses have not been appropriately evaluated upon concomitant delivery of these vaccines. Therefore, we performed an open label, non-randomized clinical trial studying the safety and immunogenicity following concomitant delivery of the Yellow fever virus (YFV) vaccine with Tick-borne encephalitis virus (TBEV) and Japanese encephalitis virus (JE) virus vaccines.Methods and findingsFollowing screening, healthy study subjects were enrolled into different cohorts receiving either TBEV and YFV vaccines, JEV and YFV vaccines, or in control groups receiving only the TBEV, JEV, or YFV vaccine. Concomitant delivery was given in the same or different upper arms for comparison in the co-vaccination cohorts. Adverse effects were recorded throughout the study period and blood samples were taken before and at multiple time-points following vaccination to evaluate immunological responses to the vaccines. Adverse events were predominantly mild in the study groups. Four serious adverse events (SAE) were reported throughout the trial, none of them deemed related to vaccination. The development of neutralizing antibodies (nAbs) against TBEV, JEV, or YFV was not affected by the concomitant vaccination strategy. Concomitant vaccination in the same or different upper arms did not significantly affect safety or immunogenicity-related outcomes. Exploratory studies on immunological effects were additionally performed and included studies of lymphocyte activation, correlates associated with germinal center activation, and plasmablast expansion.ConclusionsInactivated TBEV or JEV vaccines can be co-administered with the live attenuated YFV vaccine without an increased risk of adverse events and without reduced development of nAbs to the respective viruses. The vaccines can be delivered in the same upper arm without negative outcome.Trial registrationEudra CT 2017-002137-32Author summaryWhy was this study done?Flavivirus infections pose a significant global health burden, underscoring the need for the development of safe and efficient vaccination strategiesCo-administration of different flavivirus vaccines saves time and visits to health care units and vaccine clinics. It serves to provide protection against multiple pathogens in a shorter time-span, both for individuals living in or travelling to endemic areasSafety and immunogenicity-related responses have not been appropriately evaluated upon co-administration of many vaccines including currently used flavivirus vaccines, such as Yellow fever virus (YFV), Tick-borne encephalitis virus (TBEV), and Japanese encephalitis virus (JE) virus vaccinesBecause of this, we performed an open label, non-randomized clinical trial studying the safety and immunogenicity following co-administration of YFV vaccine with TBEV and JEV vaccinesWhat did the researchers find?Adverse events, neutralizing antibodies (nAbs) and other related immunological parameters were not adversely affected by concomitant delivery of the vaccinesConcomitant vaccination in the same versus different upper arms of study participants did not significantly affect safety or immunogenicity outcomesWhat do these findings mean?Co-administration of YFV vaccine and TBEV or JEV vaccines is feasible without increased risk of adverse events or reduced development of nAbs against the respective viruses. Furthermore, the vaccines can safely be delivered in the same upper arm without negative outcome