Discussion
YFV, TBEV
COLD SYMPTOMS
Here, we report the results of an open label, non-randomized, academic clinical trial assessing the safety and immunogenicity upon concomitant vaccination with different commonly used flavivirus vaccines. Healthy study participants were enrolled into cohorts receiving vaccines against TBEV and YFV in different or the same upper arm, JEV and YFV in different or the same upper arm, and in control cohorts receiving vaccines against TBEV, JEV, or YFV. Co-administration of the TBEV or JEV vaccine with the YFV vaccine was well tolerated with respect to reported AEs. Clinical virology, chemistry, and immunological assessments supported these conclusions with no markedly unexpected responses observed. Serological responses including virus-specific IgG levels and virus-specific nAb titers towards individual viruses were not adversely affected by concomitant vaccination. Additional immunological studies added deeper immunological insights into vaccine responses in concomitantly vaccinated study participants and controls.Of the AEs reported following vaccination, the majority were mild, dominated by common cold symptoms followed by classical reactogenicity-related responses. The majority of the reported AEs were deemed unrelated to vaccination. AEs related to vaccination (deemed possible or probable) were in line with previous safety data of single vaccination studies and the manufacturer’s reported known side effects [Earlier studies have shown the possible enhancement of cross-reactive flavivirus cellular and humoral immunity after flavivirus vaccinations [In addition to assessing the effect of concomitant vaccination on serological outcomes, we also assessed effects on lymphocyte activation and, in more detail, germinal center and plasmablast responses. As expected, NK cell, T cell, and B cell activation was observed in the cohorts receiving the live attenuated YFV vaccine (cohorts A1, A2, B1, B2 and E) in line with previous research [Co-administration of vaccines into the same or different upper arms allowed for comparative studies between these different strategies of administering two different vaccines. One advantage with administrating vaccines in the same upper arm (or at the same site in general) is that the other upper arm is not affected in terms of local reactogenicity responses. That may save the dominant arm from possible functional impairment over the first days following vaccination. As mentioned, no statistically significant differences between the study and control cohorts’ TNF or IL-18 serum comparing cohorts A1 with A2 or B1 with B2 were observed. Similarly, no statistical differences were found in terms of the development of virus-specific nAbs between the A1 and A2 or B1 and B2 cohorts as well as other B cell-related responses including activation and plasmablasts expansion. The only observed statistically significant difference noted between the same arm (A2 and B2) and different arm (A1 and B1) concomitant vaccine cohorts was the frequency of activated CD4The relative strength of the present study is that data were collected from a Concomitant vaccine administration strategies have been used in child vaccination programs [In conclusion, this clinical trial showed that concomitant TBEV or JEV vaccination with the live attenuated YFV vaccine is associated with little risk of SAE and, additionally, does not associated with any impairment on the development of nAbs to the respective viruses. Finally, the vaccines can readily be administered in the same upper arm. The present findings may be relevant for simultaneous administration of live and inactivated flavivirus vaccines in general, and also in context of the shared antigenic relationships of these agents.