Effective induction of high-titer antibodies by viral vector vaccines

Draper, Simon J.; Moore, Anne; Goodman, Anna; Long, Carole A.; Holder, Anthony A.; Gilbert, Sarah C.; Hill, Fergal; Hill, Adrian V. S.

doi:10.1038/nm.1850

Cited by 144 publications

(263 citation statements)

References 16 publications

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“…This finding is consistent with that for a similar prime/boost regimen reported by Draper et al; 45 their study focused on humoral immunity against malaria; it is also in agreement with the finding reported by Santra et al, 22 who focused on cell-mediated immunity against HIV in a monkey model.…”

Section: Prophylactic Vaccine H-b Wang Et Alsupporting

confidence: 92%

Partial protection against SIV challenge by vaccination of adenovirus and MVA vectors in rhesus monkeys

Kondo

Yoshida

et al. 2009

Gene Ther

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This study explores the effect of priming rhesus monkeys with an Ad5/35 vector expressing simian immunodeficiency virus (SIV) gag and gp120, and then boosting the animals with an modified vaccinia virus Ankara (MVA) vector encoding the same antigens after a 2-month interval. The animals were intravenously challenged with 100 TCID50 of highly pathogenic SIVmac239 virus 2 months after the booster vaccination. The priming vaccination induced robust SIV-specific cell-mediated and humoral immune responses, and boosting further enhanced the cellular immunity. Vaccination reduced peak and long-term viral loads by 1-2 logs for a period of 46 months, as reflected by a reduction in both the SIV RNA and DNA levels. Of considerable interest, the immunized monkeys did not suffer from loss of CD4 T cells, particularly central memory CD4 T cells. These results demonstrate that prophylactic vaccination with Ad5/35 followed by MVA reduces viral replication and prevents CD4 T-cell loss, and that these effects may decrease the likelihood of disease progression.

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Section: Prophylactic Vaccine H-b Wang Et Alsupporting

confidence: 92%

Partial protection against SIV challenge by vaccination of adenovirus and MVA vectors in rhesus monkeys

Kondo

Yoshida

et al. 2009

Gene Ther

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“…These vaccines were developed with the aim of providing a broad immunological response that can protect against multiple strains of P. falciparum. The use of a ChAd63 vector to prime responses followed by a boost with MVA 8 wk later has been shown to induce high levels of T cells and substantial Ab responses in both animal models and phase I/IIa clinical trials in humans for both blood-stage vaccine candidate Ags (8,24,25). However, previous studies have raised concerns that inclusion of multiple allelic variants in a vaccine may be detrimental to both the priming and in vivo restimulation of Ag-experienced memory T cells owing to the immune evasion effects of antagonistic APLs present in polymorphic Ags.…”

Section: Discussionmentioning

confidence: 99%

“…These two Ags have been associated with protective immunity in naturally exposed individuals (5-7), as well as proving efficacious in preclinical vaccine studies of mice (8)(9)(10) and nonhuman primates (11)(12)(13)(14). Although protective blood-stage immunity has been widely associated with Ab responses, a growing body of evidence in both animal and human studies supports a contributing role for cellular immunity (15,16).…”

mentioning

confidence: 99%

Assessment of Immune Interference, Antagonism, and Diversion following Human Immunization with Biallelic Blood-Stage Malaria Viral-Vectored Vaccines and Controlled Malaria Infection

Elias

Collins

Halstead

et al. 2013

The Journal of Immunology

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Overcoming antigenic variation is one of the major challenges in the development of an effective vaccine against Plasmodium falciparum, a causative agent of human malaria. Inclusion of multiple antigen variants in subunit vaccine candidates is one strategy that has aimed to overcome this problem for the leading blood-stage malaria vaccine targets, merozoite surface protein 1 (MSP1) and apical membrane antigen 1 (AMA1). However previous studies, utilizing malaria antigens, have concluded that inclusion of multiple allelic variants, encoding altered peptide ligands (APL), in such a vaccine may be detrimental to both the priming and in vivo re-stimulation of antigen-experienced T cells. Here we analyze the T cell responses to two alleles of MSP1 and AMA1 induced by vaccination of malaria-naïve adult volunteers with bi-valent viral vectored vaccine candidates. We show a significant bias to the 3D7/MAD20 allele compared to the Wellcome allele for the 33kDa region of MSP1, but not for the 19kDa fragment or the AMA1 antigen. Whilst this bias could be caused by ‘immune interference’ at priming, the data don’t support a significant role for ‘immune antagonism’ during memory T cell re-stimulation, despite observation of the latter at a minimal epitope level in vitro. A lack of class I HLA epitopes in the Wellcome allele that are recognized by vaccinated volunteers may in fact contribute to the observed bias. We also show that controlled infection with 3D7 strain P. falciparum parasites neither boosts existing 3D7-specific T cell responses nor appears to ‘immune divert’ cellular responses towards the Wellcome allele.

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“…In recent years, viral-vectored blood-stage malaria vaccines have also been developed (7,8). Heterologous primeboost immunization regimens, involving replication-defective adenoviruses of human or simian serotype or the orthopoxvirusmodified vaccinia virus Ankara (MVA), have shown particular promise in mice and rabbits (9)(10)(11). These vectored vaccines can induce qualitatively different types of immune responses to protein-in-adjuvant vaccines, including high-titer Th1 isotypeskewed Ab responses and, most notably, strong T cell responses (9).…”

mentioning

confidence: 99%

“…Heterologous primeboost immunization regimens, involving replication-defective adenoviruses of human or simian serotype or the orthopoxvirusmodified vaccinia virus Ankara (MVA), have shown particular promise in mice and rabbits (9)(10)(11). These vectored vaccines can induce qualitatively different types of immune responses to protein-in-adjuvant vaccines, including high-titer Th1 isotypeskewed Ab responses and, most notably, strong T cell responses (9). Abs induced by such regimens in mice and rabbits against MSP1 and AMA1 were shown to inhibit the growth of P. falciparum in vitro (10,11), and vaccination with an adenovirus-MVA regimen can protect mice against a lethal challenge with bloodstage P. yoelii (9).…”

mentioning

confidence: 99%

Enhancing Blood-Stage Malaria Subunit Vaccine Immunogenicity in Rhesus Macaques by Combining Adenovirus, Poxvirus, and Protein-in-Adjuvant Vaccines

Draper

Biswas

Spencer

et al. 2010

The Journal of Immunology

109

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Protein-in-adjuvant formulations and viral-vectored vaccines encoding blood-stage malaria Ags have shown efficacy in rodent malaria models and in vitro assays against Plasmodium falciparum. Abs and CD4+ T cell responses are associated with protective efficacy against blood-stage malaria, whereas CD8+ T cells against some classical blood-stage Ags can also have a protective effect against liver-stage parasites. No subunit vaccine strategy alone has generated demonstrable high-level efficacy against blood-stage infection in clinical trials. The induction of high-level Ab responses, as well as potent T and B cell effector and memory populations, is likely to be essential to achieve immediate and sustained protective efficacy in humans. This study describes in detail the immunogenicity of vaccines against P. falciparum apical membrane Ag 1 in rhesus macaques (Macaca mulatta), including the chimpanzee adenovirus 63 (AdCh63), the poxvirus modified vaccinia virus Ankara (MVA), and protein vaccines formulated in Alhydrogel or CoVaccine HT adjuvants. AdCh63-MVA heterologous prime-boost immunization induces strong and long-lasting multifunctional CD8+ and CD4+ T cell responses that exhibit a central memory-like phenotype. Three-shot (AdCh63-MVA-protein) or two-shot (AdCh63-protein) regimens induce memory B cells and high-titer functional IgG responses that inhibit the growth of two divergent strains of P. falciparum in vitro. Prior immunization with adenoviral vectors of alternative human or simian serotype does not affect the immunogenicity of the AdCh63 apical membrane Ag 1 vaccine. These data encourage the further clinical development and coadministration of protein and viral vector vaccine platforms in an attempt to induce broad cellular and humoral immune responses against blood-stage malaria Ags in humans.

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Effective induction of high-titer antibodies by viral vector vaccines

Cited by 144 publications

References 16 publications

Partial protection against SIV challenge by vaccination of adenovirus and MVA vectors in rhesus monkeys

Partial protection against SIV challenge by vaccination of adenovirus and MVA vectors in rhesus monkeys

Assessment of Immune Interference, Antagonism, and Diversion following Human Immunization with Biallelic Blood-Stage Malaria Viral-Vectored Vaccines and Controlled Malaria Infection

Enhancing Blood-Stage Malaria Subunit Vaccine Immunogenicity in Rhesus Macaques by Combining Adenovirus, Poxvirus, and Protein-in-Adjuvant Vaccines

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