Neutralizing antibody to Mengo virus, induced by synthetic peptides

Muir, Susie; Weintraub, Jory P.; Hogle, James M.; Bittle, James L.

doi:10.1099/0022-1317-72-5-1087

Cited by 11 publications

(11 citation statements)

References 21 publications

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“…To our knowledge, this is the first study demonstrating that picornavirus-specific CD4 ϩ T cells mediate protection against virus challenge in the natural host. T-cell-specific protection is achieved in the absence of prophylactic levels of serum neutralizing antibodies and contrasts the long-standing picornavi-rus paradigm that host protection is afforded by neutralizing antibodies (5,16,31,40). Adoptive transfer of vMC 24 -specific bulk-cultured CD4 ϩ T cells to naive mice protects against EMCV-induced lethal encephalomyelitis.…”

Section: Discussionmentioning

confidence: 95%

“…Mice are highly susceptible to cardiovirus infections (11,36), resulting in acute neurotropic disease producing rapid and lethal meningoencephalomyelitis (19,52). The ability to protect mice against cardiovirus-induced disease by the elicitation or passive transfer of neutralizing antibodies is well documented (5,16,31,40). Mice immunized with an attenuated strain of mengovirus (vMC 24 ) elicit high serum neutralizing antibody titers and are protected from lethal EMCV challenge (13).…”

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confidence: 99%

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Picornavirus-specific CD4+ T lymphocytes possessing cytolytic activity confer protection in the absence of prophylactic antibodies

Neal

Splitter

1995

J Virol

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Picornaviruses are a family of positive-strand RNA viruses that are responsible for a variety of devastating human and animal diseases. An attenuated strain of mengovirus (vMC 24 ) is serologically indistinguishable from the lethal murine wild-type mengovirus and encephalomyocarditis virus (EMCV). Immunogen-specific stimulation of vMC 24 -immune splenocytes in vitro demonstrates preferential activation of CD4 ؉ lymphocytes. vMC 24 -immune splenocytes adoptively transferred to naive recipients conferred protection against lethal EMCV challenge. Immune splenocytes, expanded in vitro, were >92% CD4 ؉ T lymphocytes. Interestingly, adoptive transfer of these expanded cells engendered protection against lethal challenge. In vivo depletion of CD4 ؉ T lymphocytes prior to lethal challenge abrogated survival of transfer recipients, confirming that CD4 ؉ T lymphocytes were essential for protection. Subsequent rechallenge of vMC 24 -immune splenocyte recipients with a greater EMCV dose elicited serum neutralizing antibody titers paralleling the high titers observed in vMC 24 -immunized mice. Unexpectedly, an augmented humoral response was absent in vMC 24 -specific CD4 ؉ T-cell recipients after the secondary challenge. Moreover, comparably low serum neutralizing antibody titers failed to protect passive transfer recipients when correspondingly challenged. vMC 24 -immune splenocytes expanded in vitro (>94% CD4 ؉ ) lysed vMC 24 -infected A20.J target cells. The ability to transfer protection with primed CD4 ؉ T cells, in the absence of primed B lymphocytes or immune sera, is novel for picornaviral infections. Consequently, mechanisms such as CD4 ؉ cytolytic T-lymphocyte activity are implicated in mediating protection.

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Section: Discussionmentioning

confidence: 95%

mentioning

confidence: 99%

Picornavirus-specific CD4+ T lymphocytes possessing cytolytic activity confer protection in the absence of prophylactic antibodies

Neal

Splitter

1995

J Virol

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“…Recently, neutralizing antibodies against poliovirus [25], foot-and-mouth disease virus [26], mengo virus [27] or HIV [28, 291 have been induced by immunization with monomeric or polymeric synthetic peptides containing defined B or Tcell epitopes. This approach represents a very promising approach to develop efficient and safe vaccines [30].…”

Section: Discussionmentioning

confidence: 99%

Stimulation of a memory B cell response does not require primed helper T cells

et al. 1995

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The use of universally immunogenic T cell epitopes, such as those identified in tetanus toxin or malaria circumsporozoite protein, could represent a major improvement in the development of synthetic vaccines. However, one limitation of this approach is the lack of T cell cross-reactivity between the vaccine and the pathogen. To determine whether the memory B cell response elicited by immunization with a synthetic peptide containing a B cell epitope linked to a T cell epitope can be restimulated by the same B cell epitope linked to different T cell epitope(s), we used a synthetic peptide which contains non-overlapping B and T cell determinants from hepatitis B surface antigen (HBsAg) of hepatitis B virus (HBV). The results of this study clearly show that primed T cells can increase the antibody response against a B cell epitope linked to the priming T cell determinant. However, the antibody response obtained was weaker than that obtained after two injections of the peptide containing both B and T cell epitopes, showing the important role played by memory B cells in secondary antibody responses. Moreover, a strong antibody response against the B cell epitope was elicited by boosting mice with the B cell epitope linked to a heterologous carrier, thus demonstrating that a strong B cell memory response can be revealed in the absence of primed T cells. These results therefore provide new important information for the design of synthetic or recombinant vaccines.

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“…We have selected defined dominant epitopes from vesicular stomatitis virus (VSV) (7), respiratory syncytial virus (RSV) (22), mengovirus (24), Sendai virus (SV) (9), and lymphocytic choriomeningitis virus (LCMV) (20) and a promiscuous epitope, immunogenic on several MHC backgrounds, from the bacterium Mycobacterium tuberculosis (MTB epitope) (33). These six epitopes have been fused together, with a single start codon and no intervening amino acids.…”

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confidence: 99%

A multivalent minigene vaccine, containing B-cell, cytotoxic T-lymphocyte, and Th epitopes from several microbes, induces appropriate responses in vivo and confers protection against more than one pathogen

Whitton

1997

J Virol

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The development of safe and effective vaccines remains a major goal in the prevention, and perhaps treatment, of infectious diseases. Ideally, a single vaccine would confer protection against several pathogens and would induce both cellular and humoral arms of the immune response. We originally demonstrated that two virus-specific cytotoxic T-lymphocyte (CTL) epitopes, from the same virus but presented by different major histocompatibility complex alleles, when linked in tandem as minigenes in a recombinant vaccinia virus, could confer complete protection against subsequent viral challenge. In the study, we extended this approach, which we termed string of beads, expanding the immunogenic scope in two ways: first, by introduction of T helper (T h ) and B-cell (antibody) epitopes alongside CTL epitopes and second, by including immunogenic sequences from a variety of infectious agents, five viruses and one bacterium. The vaccine (VV-sv) comprises CTL epitopes from Sendai virus, respiratory syncytial virus, and lymphocytic choriomeningitis virus (LCMV); T h epitopes from vesicular stomatitis virus and Mycobacterium tuberculosis;and an antibody epitope from mengovirus. The construct contains a single start codon, and the epitopes are linked directly, without intervening spacer amino acids. There was some concern that the combination of several normally immunodominant epitopes might result in a new hierarchy of dominance, in which certain epitopes predominated and others exhibited reduced immunogenicity. However we show that when analyzed in tissue culture and in vivo, all six epitopes are expressed. CTL and T h cells are induced in vivo, along with neutralizing antibody. The induced immunity is biologically relevant: after VV-sv immunization, the antimengovirus antibody confers protection against mengovirus challenge. Similarly, CTL induced by the LCMV epitope protected mice against challenge with this agent. Thus, a polyvalent, minigene-based vaccine can simultaneously induce several classes of immune response and thereby can confer protection against diverse pathogens.

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Neutralizing antibody to Mengo virus, induced by synthetic peptides

Cited by 11 publications

References 21 publications

Picornavirus-specific CD4+ T lymphocytes possessing cytolytic activity confer protection in the absence of prophylactic antibodies

Picornavirus-specific CD4+ T lymphocytes possessing cytolytic activity confer protection in the absence of prophylactic antibodies

Stimulation of a memory B cell response does not require primed helper T cells

A multivalent minigene vaccine, containing B-cell, cytotoxic T-lymphocyte, and Th epitopes from several microbes, induces appropriate responses in vivo and confers protection against more than one pathogen

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