Swine Influenza Virus Vaccine: Potentiation of Antibody Responses in Rhesus Monkeys

Stephen, Edward L.; Hilmas, Duane E.; Mangiafico, JA; Levy, Harold B.

doi:10.1126/science.408923

Cited by 31 publications

(13 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Synthetic double-stranded RNAs lead to enhanced B-cell activation and antibody production in mice (34) and also NHPs (32,33,35,36). We confirmed these findings, but surprisingly, we found that the avidity of Gag-specific antibodies was lower with the DEC-targeted vaccine.…”

Section: Cd8supporting

confidence: 81%

Immunization with HIV Gag targeted to dendritic cells followed by recombinant New York vaccinia virus induces robust T-cell immunity in nonhuman primates

Flynn

Kastenmüller²,

Wille-Reece³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

122

108

View full text Add to dashboard Cite

Protein vaccines, if rendered immunogenic, would facilitate vaccine development against HIV and other pathogens. We compared in nonhuman primates (NHPs) immune responses to HIV Gag p24 within 3G9 antibody to DEC205 (“DEC-HIV Gag p24”), an uptake receptor on dendritic cells, to nontargeted protein, with or without poly ICLC, a synthetic double stranded RNA, as adjuvant. Priming s.c. with 60 μg of both HIV Gag p24 vaccines elicited potent CD4 + T cells secreting IL-2, IFN-γ, and TNF-α, which also proliferated. The responses increased with each of three immunizations and recognized multiple Gag peptides. DEC-HIV Gag p24 showed better cross-priming for CD8 + T cells, whereas the avidity of anti-Gag antibodies was ∼10-fold higher with nontargeted Gag 24 protein. For both protein vaccines, poly ICLC was essential for T- and B-cell immunity. To determine whether adaptive responses could be further enhanced, animals were boosted with New York vaccinia virus (NYVAC)-HIV Gag/Pol/Nef. Gag-specific CD4 + and CD8 + T-cell responses increased markedly after priming with both protein vaccines and poly ICLC. These data reveal qualitative differences in antibody and T-cell responses to DEC-HIV Gag p24 and Gag p24 protein and show that prime boost with protein and adjuvant followed by NYVAC elicits potent cellular immunity.

show abstract

Section: Cd8supporting

confidence: 81%

Immunization with HIV Gag targeted to dendritic cells followed by recombinant New York vaccinia virus induces robust T-cell immunity in nonhuman primates

Flynn

Kastenmüller²,

Wille-Reece³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

122

108

View full text Add to dashboard Cite

show abstract

“…Poly ICLC possesses anti-viral activity against a variety of viruses in monkeys [31]–[33] and chimpanzees [34], and also inhibits malaria infection of macaques [35]. Furthermore, it has shown potent adjuvant activity on the induction of humoral immune responses in the nonhuman primate models of Venezuelan equine encephalomyelitis virus and swine influenza virus [36],[37]. In humans, dose-dependently, mild to moderate side effects of poly ICLC were observed in a number of phase I and II studies conducted in children and adults [38]–[45].…”

Section: Introductionmentioning

confidence: 99%

Synthetic Double-Stranded RNAs Are Adjuvants for the Induction of T Helper 1 and Humoral Immune Responses to Human Papillomavirus in Rhesus Macaques

et al. 2009

View full text Add to dashboard Cite

Toll-like receptor (TLR) ligands are being considered as adjuvants for the induction of antigen-specific immune responses, as in the design of vaccines. Polyriboinosinic-polyribocytoidylic acid (poly I:C), a synthetic double-stranded RNA (dsRNA), is recognized by TLR3 and other intracellular receptors. Poly ICLC is a poly I:C analogue, which has been stabilized against the serum nucleases that are present in the plasma of primates. Poly I:C12U, another analogue, is less toxic but also less stable in vivo than poly I:C, and TLR3 is essential for its recognition. To study the effects of these compounds on the induction of protein-specific immune responses in an animal model relevant to humans, rhesus macaques were immunized subcutaneously (s.c.) with keyhole limpet hemocyanin (KLH) or human papillomavirus (HPV)16 capsomeres with or without dsRNA or a control adjuvant, the TLR9 ligand CpG-C. All dsRNA compounds served as adjuvants for KLH-specific cellular immune responses, with the highest proliferative responses being observed with 2 mg/animal poly ICLC (p = 0.002) or 6 mg/animal poly I:C12U (p = 0.001) when compared with immunization with KLH alone. Notably, poly ICLC—but not CpG-C given at the same dose—also helped to induce HPV16-specific Th1 immune responses while both adjuvants supported the induction of strong anti-HPV16 L1 antibody responses as determined by ELISA and neutralization assay. In contrast, control animals injected with HPV16 capsomeres alone did not develop substantial HPV16-specific immune responses. Injection of dsRNA led to increased numbers of cells producing the T cell–activating chemokines CXCL9 and CXCL10 as detected by in situ hybridization in draining lymph nodes 18 hours after injections, and to increased serum levels of CXCL10 (p = 0.01). This was paralleled by the reduced production of the homeostatic T cell–attracting chemokine CCL21. Thus, synthetic dsRNAs induce an innate chemokine response and act as adjuvants for virus-specific Th1 and humoral immune responses in nonhuman primates.

show abstract

“…Further studies of polyIC showed that it was rapidly broken down in the plasma of humans and nonhuman primates, but it was much more stable when complexed with polylysine, as polyICLC. Toxicity thresholds for rhesus macaques were investigated in three studies (Levy et al, 1975;Sammons et al, 1977;Stephen et al, 1977a). …”

Section: Experimental Infections Of Nhps With Human Influenza VImentioning

confidence: 99%

“…A 1969 study showed that antibody responses of AGMs to a quadrivalent killed vaccine were markedly enhanced if the vaccine was emulsified in peanut oil, or if the oligonucleotide polyIC was added to the inoculum (Woodhour et al, 1969). Similarly, when a swine-origin H1N1 virus emerged in 1976, it was found that adding polyICLC markedly enhanced antibody responses of rhesus macaques to a subunit vaccine (Stephen et al, 1977a). …”

Section: Experimental Infections Of Nhps With Human Influenza VImentioning

confidence: 99%

The use of nonhuman primates in research on seasonal, pandemic and avian influenza, 1893–2014

2015

View full text Add to dashboard Cite

Attempts to reproduce the features of human influenza in laboratory animals date from the early 1890s, when Richard Pfeiffer inoculated apes with bacteria recovered from influenza patients and produced a mild respiratory illness. Numerous studies employing nonhuman primates (NHPs) were performed during the 1918 pandemic and the following decade. Most used bacterial preparations to infect animals, but some sought a filterable agent for the disease. Since the viral etiology of influenza was established in the early 1930s, studies in NHPs have been supplemented by a much larger number of experiments in mice, ferrets and human volunteers. However, the emergence of a novel swine-origin H1N1 influenza virus in 1976 and the highly pathogenic H5N1 avian influenza virus in 1997 stimulated an increase in NHP research, because these agents are difficult to study in naturally infected patients and cannot be administered to human volunteers. In this paper, we review the published literature on the use of NHPs in influenza research from 1893 through the end of 2014. The first section summarizes observational studies of naturally occurring influenza-like syndromes in wild and captive primates, including serologic investigations. The second provides a chronological account of experimental infections of NHPs, beginning with Pfeiffer’s study and covering all published research on seasonal and pandemic influenza viruses, including vaccine and antiviral drug testing. The third section reviews experimental infections of NHPs with avian influenza viruses that have caused disease in humans since 1997. The paper concludes with suggestions for further studies to more clearly define and optimize the role of NHPs as experimental animals for influenza research.

show abstract

Swine Influenza Virus Vaccine: Potentiation of Antibody Responses in Rhesus Monkeys

Cited by 31 publications

References 9 publications

Immunization with HIV Gag targeted to dendritic cells followed by recombinant New York vaccinia virus induces robust T-cell immunity in nonhuman primates

Immunization with HIV Gag targeted to dendritic cells followed by recombinant New York vaccinia virus induces robust T-cell immunity in nonhuman primates

Synthetic Double-Stranded RNAs Are Adjuvants for the Induction of T Helper 1 and Humoral Immune Responses to Human Papillomavirus in Rhesus Macaques

The use of nonhuman primates in research on seasonal, pandemic and avian influenza, 1893–2014

Contact Info

Product

Resources

About