Protective CD4⁺and CD8⁺T Cells against Influenza Virus Induced by Vaccination with Nucleoprotein DNA

Abstract

DNA vaccination is an effective means of eliciting both humoral and cellular immunity, including cytotoxic T lymphocytes (CTL). Using an influenza virus model, we previously demonstrated that injection of DNA encoding influenza virus nucleoprotein (NP) induced major histocompatibility complex class I-restricted CTL and cross-strain protection from lethal virus challenge in mice (J. B. Ulmer et al., Science 259:1745–1749, 1993). In the present study, we have characterized in more detail the cellular immune responses induced by NP DNA, which included robust lymphoproliferation and Th1-type cytokine secretion (high levels of gamma interferon and interleukin-2 [IL-2], with little IL-4 or IL-10) in response to antigen-specific restimulation of splenocytes in vitro. These responses were mediated by CD4+ T cells, as shown by in vitro depletion of T-cell subsets. Taken together, these results indicate that immunization with NP DNA primes both cytolytic CD8+ T cells and cytokine-secreting CD4+ T cells. Further, we demonstrate by adoptive transfer and in vivo depletion of T-cell subsets that both of these types of T cells act as effectors in protective immunity against influenza virus challenge conferred by NP DNA.

Comparative Efficacy of Hemagglutinin, Nucleoprotein, and Matrix 2 Protein Gene-Based Vaccination against H5N1 Influenza in Mouse and Ferret

“…While the hemagglutinin (HA) surface protein is conventionally the primary target of strain-specific influenza DNA vaccines, conserved viral epitopes have the potential to induce immunity against diverse influenza strains. Two highly conserved influenza viral proteins, NP and M2, have been widely targeted as possible broadly protective vaccine candidates [1][2][3][4][5][6][7][8][9]. The main function of the nucleoprotein is encapsidation of the viral genome to form a ribonucleoprotein particle for transcription and packaging.…”

Partial protection against H5N1 influenza in mice with a single dose of a chimpanzee adenovirus vector expressing nucleoprotein

“…This is due to the relatively low rate of drift in the NP sequence [5]. Active protection of mice from a lethal challenge with heterotypic influenza A following DNA vaccination with NP has been demonstrated [6]; this protection could be adoptively transferred to naïve mice by CD4 + or CD8 + T cells from immunized mice [7]. Adenoviral vaccines are especially efficient in eliciting strong T cell responses against products of the transgene.…”

Induction of SARS-nucleoprotein-specific immune response by use of DNA vaccine

“…Some reports demonstrated that protective responses elicited by antigens of some viruses that were not present on the surface of the virion, such as the N protein, were more likely to be due to CTLs. For example, nucleoproteins of Ebola virus [4,5], measles virus [6], lymphocytic choriomeningitis virus [7] and influenza virus [8,9] may induce protective CTLs. In porcine coronavirus, transmissible gastroenteritis virus (TGEV), N protein is a representative antigen for the T-cell response and may induce cellular and humoral immune response [10].…”