In conclusion, our evidence support current efforts to develop PAM-specific vaccines based on VAR2CSA and highlight the versatility of human monoclonal antibodies generated from clinically immune donors in these investigations. Stimulation of ribosomal frameshifting by antisense LNA Programmed ribosomal frameshifting is a translational recoding mechanism commonly used by RNA viruses to express two or more proteins from a single mRNA at a fixed ratio. An essential element in this process is the presence of an RNA secondary structure, such as a pseudoknot or a hairpin, located downstream of the slippery sequence. Here, we have tested the efficiency of RNA oligonucleotides annealing downstream of the slippery sequence to induce frameshifting in vitro. Maximal frameshifting was observed with oligonucleotides of 12–18 nt. Antisense oligonucleotides bearing locked nucleid acid (LNA) modifications also proved to be efficient frameshift-stimulators in contrast to DNA oligonucleotides. The number, sequence and location of LNA bases in an otherwise DNA oligonucleotide have to be carefully manipulated to obtain optimal levels of frameshifting. Our data favor a model in which RNA stability at the entrance of the ribosomal tunnel is the major determinant of stimulating slippage rather than a specific three-dimensional structure of the stimulating RNA element. Programmed ribosomal frameshifting is a translational recoding event that increases the versatility of gene expression. It is mainly utilized by eukaryotic RNA viruses (1) (2) (3) , though some prokaryotic (4) and mammalian genes (5) (6) (7) are also controlled by ribosomal frameshifting. The requirements for À1 ribosomal frameshifting are the presence of a slippery heptanucleotide sequence X XXY YYZ (where X can be A, U, G or C; Y can be A or U; and Z does not equal Y; the spaces indicate the original reading frame) (8) followed by a downstream structural element, such as a pseudoknot, a hairpin or an antisense oligonucleotide duplex [for reviews, see (9) ]. Although the mechanism of frameshifting is still elusive, a promising model has been proposed by Brierley and co-workers using cryo-electron microscopy to image mammalian 80S ribosomes (10) . In their model, the ribosome is paused by its inability to unwind a pseudoknot structure resulting in a blockage of the A-site by eEF-2. During translocation, the P-site tRNA is bent in the 3 0 -direction by opposing forces. To release the tension, the P-site tRNA may un-pair and subsequently re-pair in the À1 frame with a certain frequency, followed by A-site tRNA delivery into the new À1 reading frame. These and other recent data obtained by mechanical unfolding of frameshifter pseudoknots suggest that mRNA secondary structures with certain conformational features that resist ribosomal helicase-mediated unwinding and eEF-2 catalyzed translocation are key players in ribosomal frameshifting.