Synthetic Recombinant Vaccines against Viral Agents

Abstract

Synthetic recombinant vaccines are expression vectors incorporating defined epitope(s) of microbial agents. They are prepared by inserting synthetic oligonucleotide(s) coding for previously identified relevant epitopes into the genome of a desired vector, using recombinant DNA technology. The results discussed indicate that immunization with such vaccines carrying viral epitopes may lead to protective immunity against viral agents. Oligonucleotides coding for three influenza epitopes stimulating B cells, T helper cells and cytotoxic lymphocytes were individually inserted into the flagellin gene of a Salmonella vaccine strain. Immunization of mice with the resultant recombinant bacteria or their isolated flagella induced a specific mucosal anti-influenza protective response. The most efficient vaccine consisted of all three recombinant flagella, administered intranasally. The protection elicited was cross-strain specific, long-lasting and efficient against a lethal viral challenge.

Effect of aging on immunocompetent and inflammatory cells

“…Oligonucleotides coding for influenza epitopes were genetically engineered into the flagellin gene of Salmonella. The recombinant bacteria or the isolated flagella stimulated a specific mucosal antiinfluenza protective response in mice (7). The most recent vaccine approach (number 4), genetic immunization, is the injection of polynucleotides (that is, complementary DNA or messenger RNA) from the pathogen either alone, on a carrier such as gold beads or in liposomes (47).…”

Intranasal administration of peptide vaccine protects human/mouse radiation chimera from influenza infection

“…Identification of conserved epitopes, shared by multiple viral strains, that stimulate antibody production, T h function and cytotoxic T lymphocytes (CTL) should lead to a more efficient vaccine. Efforts in our laboratory are towards the development of a vaccine preparation including a combination of such epitopes (4).…”

“…A synthetic recombinant anti-influenza vaccine based on three epitopes was found in our laboratory to be highly efficient in mice (5). This vaccine included a B cell epitope from the HA 91-108 which is conserved in all H3 strains and elicits anti-influenza neutralizing antibodies (6), together with a T h and CTL epitopes from the nucleoprotein (NP 55-69 and NP 147-158, respectively), which induce MHC-restricted immune responses (4,7). These epitopes were individually expressed in the flagellin of the Salmonella vaccine strain.…”

Synthetic peptide-based vaccines against influenza

“…The nucleoprotein is a conserved protein and the above epitopes were selected according to their capacity to induce anti-influenza specific cellular response [17]. Indeed, we could demonstrate that the NP 55-69 peptide when injected into mice with CFA elicited specific proliferation response in splenocytes [18], and that the CTL epitope (NP 147-158) was presented on MHC class I molecules of target (P815) cells, and these cells were subsequently recognized and killed by CTLs [19]. Another strategy for evaluating these three peptides as a vaccine was investigated; they were separately anchored into proteosomes (vesicles of the outer membrane proteins of meningococci) and then administrated intranasally to mice.…”