Antibody responses elicited through homologous or heterologous prime-boost DNA and protein vaccinations differ in functional activity and avidity

Vaine, Michael; Wang, Shixia; Hackett, Anthony; Arthos, James; Lu, Shan

doi:10.1016/j.vaccine.2010.02.006

Cited by 87 publications

(86 citation statements)

References 30 publications

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“…Previously, we reported that DNA prime-protein boost could induce improved antibody responses targeting the CD4bs, as such sera could compete well against the broad neutralizing mAb, b12 (Vaine, Wang et al, 2008;Vaine, Wang et al, 2010). In the current study, the presence of CD4bs-specific antibodies in rabbit immune sera was also evaluated against the broadly neutralizing antibodies b12, VRC01 and VRC03.…”

Section: Resultsmentioning

confidence: 99%

“…This result confirmed our previous data that a CD4 binding site antibody, similar to b12, was elicited in rabbit studies using gp120 immunogens from subtypes other than subtype BC. 9,11 At the same time, rabbit sera elicited by subtype BC gp120 were unable to compete against VRC01 or VRC03. This finding is not completely unexpected as VRC01 or VRC03 has much broader neutralizing activities than b12 and b12 can only neutralizing viruses from certain subtypes.…”

Section: Discussionmentioning

confidence: 99%

“…Previously, we demonstrated that priming immunizations with DNA vaccines expressing Env antigens can significantly enhance the quality, especially the neutralizing activities, of antibody responses elicited by subunit Env protein vaccines [7][8][9][10][11] ReseaRcH papeR ReseaRcH papeR of the same subtype and whether the DNA priming step is helpful for further improving the quality of antibody responses.…”

Section: Introductionmentioning

confidence: 99%

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DNA prime-protein boost using subtype consensus Env was effective in eliciting neutralizing antibody responses against subtype BC HIV-1 viruses circulating in China

Zhang

et al. 2012

Human Vaccines & Immunotherapeutics

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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DNA prime-protein boost using subtype consensus Env was effective in eliciting neutralizing antibody responses against subtype BC HIV-1 viruses circulating in China

Zhang

et al. 2012

Human Vaccines & Immunotherapeutics

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“…Moreover, vaccinations in which DNA priming is followed by a recombinant viral vaccine boost can elicit greater immunity when compared to the use of single immunogens (Lu, 2009;Radaelli et al, 2003;Radaelli et al, 2007;Wang et al, 2008). Combined vaccines can also elicit improved antigen-specific antibody responses (Vaine et al, 2010).…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

Protection of mice against the highly pathogenic VVIHD-J by DNA and fowlpox recombinant vaccines, administered by electroporation and intranasal routes, correlates with serum neutralizing activity

et al. 2016

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Please cite this article as: Bissa, M., Quaglino, E., Zanotto, C., Illiano, E., Rolih, V., Pacchioni, S., Cavallo, F., De Giuli Morghen, C., Radaelli, A., Protection of mice against the highly pathogenic VV IHD-J by DNA and fowlpox recombinant vaccines, administered by electroporation and intranasal routes, correlates with serum neutralizing activity, Antiviral Research (2016Research ( ), doi: 10.1016Research ( / j.antiviral.2016 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. and fowlpox (FP) recombinants that expressed the VV L1R, A27L, A33R, and B5R genes were generated (4DNAmix, 4FPmix, respectively) and tested in mice using novel administration routes. Mice were primed with 4DNAmix by electroporation, and boosted with 4FPmix applied intranasally. The lethal VV IHD-J strain was then administered by intranasal challenge. All of the mice receiving 4DNAmix followed by 4FPmix, and 20% of the mice immunized only with 4FPmix, were protected. The induction of specific humoral and cellular immune responses directly correlated with this protection. In particular, higher anti-A27antibodies and IFNγ-producing T lymphocytes were measured in the blood and spleen of the protected mice, as compared to controls. VV IHD-J neutralizing antibodies in sera from the protected mice suggest that the prime/ boost vaccination regimen with 4DNAmix plus 4FPmix may be an effective and safe mode to induce protection against smallpox and poxvirus zoonotic infections. The electroporation/ intranasal administration routes contributed to effective immune responses and mouse survival.

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“…A DNA prime, adenoviral serotype 5 (Ad5) vector boost vaccine expressing multiclade Env inserts elicited a greater breadth of NAbs than that of a comparator single Env immunogen (30,31). Similarly, a multiclade DNA prime, gp120 protein boost vaccine elicited a greater breadth of NAbs than that of the comparator single gp120 immunogen in rabbits (32,33). However, these previous studies did not directly compare the cocktail with each individual component of the vaccine; thus, the potential advantage of an Env immunogen cocktail remains unclear.…”

mentioning

confidence: 99%

A Multivalent Clade C HIV-1 Env Trimer Cocktail Elicits a Higher Magnitude of Neutralizing Antibodies than Any Individual Component

Bricault

Kovacs

Nkolola

et al. 2015

J Virol

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The sequence diversity of human immunodeficiency virus type 1 (HIV-1) presents a formidable challenge to the generation of an HIV-1 vaccine. One strategy to address such sequence diversity and to improve the magnitude of neutralizing antibodies (NAbs) is to utilize multivalent mixtures of HIV-1 envelope (Env) immunogens. Here we report the generation and characterization of three novel, acute clade C HIV-1 Env gp140 trimers (459C, 405C, and 939C), each with unique antigenic properties. Among the single trimers tested, 459C elicited the most potent NAb responses in vaccinated guinea pigs. We evaluated the immunogenicity of various mixtures of clade C Env trimers and found that a quadrivalent cocktail of clade C trimers elicited a greater magnitude of NAbs against a panel of tier 1A and 1B viruses than any single clade C trimer alone, demonstrating that the mixture had an advantage over all individual components of the cocktail. These data suggest that vaccination with a mixture of clade C Env trimers represents a promising strategy to augment vaccine-elicited NAb responses. IMPORTANCEIt is currently not known how to generate potent NAbs to the diverse circulating HIV-1 Envs by vaccination. One strategy to address this diversity is to utilize mixtures of different soluble HIV-1 envelope proteins. In this study, we generated and characterized three distinct, novel, acute clade C soluble trimers. We vaccinated guinea pigs with single trimers as well as mixtures of trimers, and we found that a mixture of four trimers elicited a greater magnitude of NAbs than any single trimer within the mixture. The results of this study suggest that further development of Env trimer cocktails is warranted. P rotection afforded by most currently licensed vaccines is correlated with the generation of neutralizing antibodies (NAbs) (1-3). However, no HIV-1 vaccine to date has been capable of eliciting broad and potent NAbs (4-7). Difficulties in generating broadly neutralizing antibodies (bNAbs) arise from the extensive sequence diversity of circulating strains of HIV-1 (8) and from the unusual characteristics of antibodies associated with the development of breadth (9). However, 15% of HIV-1 infected individuals develop bNAbs with substantial breadth, while over 50% of people make antibodies with at least moderate breadth, typically several years into chronic infection (10-13). Moreover, multiple broadly neutralizing monoclonal antibodies have been reported (14-17). It is therefore important to develop strategies that improve the magnitude and breadth of vaccine-elicited NAbs.As the HIV-1 Env protein is the sole viral antigen on the surface of the virus, it is the target for NAbs. HIV-1 Env is a trimer consisting of three gp120 surface subunits, responsible for interacting with the primary receptor (CD4) and the secondary receptors (CCR5 and/or CXCR4), as well as a trimer of gp41 transmembrane subunits responsible for membrane fusion (18). Previous studies have demonstrated that soluble Env gp140 trimers more closely mimic the...

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Antibody responses elicited through homologous or heterologous prime-boost DNA and protein vaccinations differ in functional activity and avidity

Cited by 87 publications

References 30 publications

DNA prime-protein boost using subtype consensus Env was effective in eliciting neutralizing antibody responses against subtype BC HIV-1 viruses circulating in China

DNA prime-protein boost using subtype consensus Env was effective in eliciting neutralizing antibody responses against subtype BC HIV-1 viruses circulating in China

Protection of mice against the highly pathogenic VVIHD-J by DNA and fowlpox recombinant vaccines, administered by electroporation and intranasal routes, correlates with serum neutralizing activity

A Multivalent Clade C HIV-1 Env Trimer Cocktail Elicits a Higher Magnitude of Neutralizing Antibodies than Any Individual Component

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