Human clinical trials have reported differing immunological outcomes following ipsilateral (same side) and contralateral (different side) vaccination. However, there is still a limited understanding of the resultant germinal centre (GC) and antibody responses following these vaccination regimens. We used adjuvanted SARS-CoV-2 spike vaccines to dissect the GC responses in draining lymph nodes and serological outcomes following prime-boost vaccination in mice. Here, mice received prime and boost immunisations 14 days apart, either ipsilaterally (twice in the left hindleg) or contralaterally (sequential left hindleg and right forelimb), with GC responses, including GC B cells (GL7+CD38lo) and memory B cells (MBC, IgD-GL7-), assessed at days 19 and 28.
Using a homologous SARS-CoV-2 WT vaccination, we identified that contralateral vaccination produced independent GC responses within draining lymph nodes. Post-boost, robust secondary GC responses were elicited in the distally draining boost site, however, the ongoing response from the primary GC was not similarly augmented. Ipsilateral vaccination resulted in a robust and sustained GC response following this vaccination regimen and accelerated the early development of antibody titres against ancestral (WT), Beta and BA.1 spike antigens at day 19. After 28 days, the magnitude, durability and neutralisation capacity of these serological responses became comparable across both ipsilateral and contralateral groups. We further utilised a heterologous SARS-CoV-2 WT/BA.1 spike prime-boost vaccination model and identified analogous GC dynamics and antibody responses as our homologous vaccination model. We identified cross-reactive GC B cells displaying differential recognition of WT and BA.1 antigens within primary or secondary GCs, depending on ipsilateral or contralateral vaccination.
Collectively, maintaining a common site for prime-boost vaccination augments MBC recall kinetics and drives higher antibody titres early in the response. This divergence between vaccination regimens is transient, however, with longer-term serological outcomes being broadly comparable.