Long-Term Maintenance of B Cell Immunity to Influenza Virus Hemagglutinin in Mice Following DNA-Based Immunization

Justewicz, D M; Webster, Robert G.

doi:10.1006/viro.1996.0501

Cited by 34 publications

(9 citation statements)

References 3 publications

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“…IgG2a antibody secreting cell levels induced in mice in response to infection with each ca donor strain were higher than other IgG subclass antibody secreting cell levels, which is consistent with serum IgG2a responses to respiratory viral infections [Fazekas et al, 1994;Sangster et al, 1995]. IgG1 and IgG2a have been shown to be the major immunoglobulin subclasses involved in virus neutralisation [Hocart et al, 1989a], although predominant IgG1 responses in BALB/c mice are usually associated with DNA vaccination rather than with resistance to live virus challenge [Justewicz and Webster, 1996]. The IgG3-speci®c antibody secreting cell response, like that of IgM, was low compared with other isotype responses (Table III).…”

Section: Discussionsupporting

confidence: 68%

Immunogenic and isotype‐specific responses to russian and US cold‐adapted influenza a vaccine donor strains A/Leningrad/134/17/57, A/Leningrad/134/47/57, and A/Ann Arbor/6/60 (H2N2) in mice

Wareing

Watson

Brooks

et al. 2001

Journal of Medical Virology

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The immunogenicity of the Russian cold-adapted (ca) donor stains, A/Leningrad (Len)/134/17/57 and A/Leningrad/134/47/57, and the US strain A/Ann Arbor (AA)/6/60-ca, were compared in BALB/c mice with their respective wild-type parental viruses. Each ca donor strain was less immunogenic than its wild-type parent. The vaccinating dose, when administered twice, which prevented multiplication of a standard challenge of parental wild-type virus in 50% of mice (the 50% protective dose or PD(50)), was shown for A/Len/134/17/57-ca, A/Len/134/47/57-ca, and A/AA/6/60-ca to be 10(3.77), 10(4.32), and 10(4.70), respectively. These findings were extended by measuring the number of antibody secreting cells induced in the lungs and mediastinal lymph nodes of mice infected with the same ca donors using an ELISPOT assay. When each donor strain was administered twice at a dose of 100 PD(50) over a 3-week interval, the overall immunoglobulin isotype antibody secreting cell profiles were shown to be similar. However, A/Len/134/17/57-ca and A/Len/134/47/57-ca induced significantly higher total immunoglobulin responses in the lungs than A/AA/6/60-ca (P < 0.05). A/Len/134/17/57-ca also induced a significantly greater IgA response in the lungs than A/AA/6/60-ca (P < 0.05). These results suggest that A/Len/134/17/57-ca is a superior immunogen to A/Len/134/47/57-ca which in turn is more immunogenic than A/AA/6/60-ca.

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Section: Discussionsupporting

confidence: 68%

Immunogenic and isotype‐specific responses to russian and US cold‐adapted influenza a vaccine donor strains A/Leningrad/134/17/57, A/Leningrad/134/47/57, and A/Ann Arbor/6/60 (H2N2) in mice

Wareing

Watson

Brooks

et al. 2001

Journal of Medical Virology

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“…DNA vaccines have the ability to induce both neutralization antibody and cell-mediated immune responses, including CTLs, and the possibility to modulate the pattern of immune responses by the route of DNA administration (Ulmer et al, 1996; Pertmer et al, 1996). Furthermore, DNA vaccines also provide long-term immunity against viruses, a highly desirable property for a practical RSV vaccine (Justewicz and Webster, 1996). DNA vaccines against RSV are under investigation and several of these induce protective immune responses (Li et al, 1998; Harcourt et al, 2004;Tree et al, 2004; Vaughan et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

RSV fusion (F) protein DNA vaccine provides partial protection against viral infection

Dennis

Pillai

et al. 2009

Virus Research

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The present study was conducted to investigate the feasibility and efficacy of a RSV F DNA vaccine incorporated with a mucosal adjuvant. Two DNA vaccine vectors (DRF-412 and DRF412-P) were developed containing residues 412-524 of the RSV F gene. These antigenic regions were cloned into the phCMV1 DNA vaccine vector. One of the DNA vaccine vectors, DRF-412, contained the ctxA2B region of the cholera toxin gene as a mucosal adjuvant. The in vitro expression of these DNA vectors were confirmed in Cos-7 cells by indirect immunofluorescence and western blot analyses. In vivo expression of the cloned gene was further confirmed in mouse muscle tissue by immunohistological analysis. The active transcription of the RSV F gene in mouse muscle cells was confirmed by RT-PCR. The purified DRF-412 and DRF412-P DNA vectors were used to immunize mice by intramuscular injections. Our results indicated that DRF-412 and DRF412-P vaccine vectors were as effective as live RSV in inducing neutralization antibody, systemic Ab (IgG, IgG1, IgG2a, and IgG2b) responses, and mucosal antibody responses (Ig A). The Th1 (TNF-α, IL-12p70, IFN-γ, IL-2) and Th2 (IL-10, IL-6) cytokine profiles were analyzed after stimulation of spleen cells from mice immunized with purified RF-412 protein. We observed that mice inoculated with vector DRF-412 induced a higher mixed Th1/Th2 cytokine immune response than DRF412-P. Reverse transcriptase and quantitative real-time PCR (qRT-PCR) revealed that mice immunized with the DRF-412 vector contained less viral RNA in lung tissue and the lung immunohistology study confirmed that mice immunized with DRF-412 had better protection than those immunized with the DRF412-P vector. These results indicate that the RSV DRF-412 vaccine vector, which contains the cholera toxin subunit ctxA2B as a mucosal adjuvant may provide a better DNA vaccination strategy against RSV.

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“…Crosslinking of the B cell receptor is a critical signal for B cell activation and results in prompt T-independent IgM response [19]. Thus, viral proteins expressed in an ordered and repetitive fashion are considerably more immunogenic than in soluble form and can even overcome B cell tolerance [20][21][22]. Further enhancement of the immune response by repetitive surfaces is provided by the fact that these structures are preferentially bound by components of the complement system and multivalent natural antibodies, resulting in enhanced phagocytosis [17].…”

Section: Repetitive Viral Structures and B-cell Responsesmentioning

confidence: 99%

Designing Recombinant Vaccines with Viral Properties: A Rational Approach to More Effective Vaccines

Jennings¹,

Bachmann²

2007

CMM

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One of the great demands and challenges for vaccination is to successfully target the pathogens responsible for much of mankind's chronic disease burden including: AIDS, infectious hepatitis, tuberculosis and malaria. Another is realizing the potential of therapeutic immunization to cure diseases such as cancer, allergy and inflammatory autoimmunity. To achieve these objectives, the fundamental insights gained from immunology, genomics, molecular-cellular biology and vaccinology must be implemented in order to develop more effective, better defined and safer vaccines. As an illustrative example of this we examine the key features of viruses that are known to be responsible for eliciting superb host immune responses. These insights have formed a basis for understanding the effectiveness of existing vaccines and provide a framework for designing and developing new vaccines better able to meet pressing unmet medical needs. The key immunogenic properties of viruses that are understood to date and are currently being applied include: their particulate nature, their highly repetitive and ordered structures, their ability to induce innate immunity with consequent conditioning of adaptive responses and the kinetics and distribution of viral antigens during infection. Vaccines and vaccine-formulations recently registered for use in humans already incorporate some of these elements. Of great anticipation is the progress of the next-generation vaccines now advancing through the various stages of research and development. Vaccines which, by way of rational design, incorporate viral properties to induce tailored responses and thus have the potential to provide safer and more effective prophylaxis and therapies.

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Long-Term Maintenance of B Cell Immunity to Influenza Virus Hemagglutinin in Mice Following DNA-Based Immunization

Cited by 34 publications

References 3 publications

Immunogenic and isotype‐specific responses to russian and US cold‐adapted influenza a vaccine donor strains A/Leningrad/134/17/57, A/Leningrad/134/47/57, and A/Ann Arbor/6/60 (H2N2) in mice

Immunogenic and isotype‐specific responses to russian and US cold‐adapted influenza a vaccine donor strains A/Leningrad/134/17/57, A/Leningrad/134/47/57, and A/Ann Arbor/6/60 (H2N2) in mice

RSV fusion (F) protein DNA vaccine provides partial protection against viral infection

Designing Recombinant Vaccines with Viral Properties: A Rational Approach to More Effective Vaccines

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