Immunogenicity profile in African green monkeys of a vaccine candidate based on a mutated form of human Interleukin-15

Abstract Background Interleukin (IL)-15 is a proinflammatory T-cell growth factor overexpressed in several autoimmune diseases such as rheumatoid arthritis. Our initial strategy to neutralize the increased levels of IL-15 consisted in a vaccine candidate based on the recombinant modified human IL-15 (mhIL-15) mixed with the alum adjuvant. A previous study in non-human primates Macaca fascicularis has shown that vaccination induces neutralizing antibodies against native IL-15, without affecting animal behavior, clinical status, or the percentage of IL-15-dependent cell populations. However, the mhIL-15 used as an antigen was active in the IL-2-dependent cytotoxic T-cell line CTLL-2, which could hinder its therapeutic application. The current article evaluated the immunogenicity in African green monkeys of a vaccine candidate based on IL-15 mutant D8SQ108S, an inactive form of human IL-15. Results IL-15 D8SQ108S was inactive in the CTLL-2 bioassay but was able to competitively inhibit the biological activity of human IL-15. Immunization with 200 µg of IL-15 mutant combined with alum elicited anti-IL-15 IgG antibodies after the second and third immunizations. The median values of anti-IL-15 antibody titers were slightly higher than those generated in animals immunized with 200 µg of mhIL-15. The highest antibody titers were induced after the third immunization in monkeys vaccinated with 350 µg of IL-15 D8SQ108S. In addition, sera from immunized animals inhibited the biological activity of human IL-15 in CTLL-2 cells. The maximum neutralizing effect was observed after the third immunization in sera of monkeys vaccinated with the highest dose of the IL-15 mutant. These sera also inhibited the proliferative activity of simian IL-15 in the CTLL-2 bioassay and did not affect the IL-2-induced proliferation of the aforementioned T-cell line. Finally, it was observed that vaccination neither affects the animal behavior nor the general clinical parameters of immunized monkeys. Conclusion Immunization with inactive IL-15 D8SQ108S mixed with alum generated neutralizing antibodies specific for human IL-15 in African green monkeys. Based on this fact, the current vaccine candidate could be more effective than the one based on biologically active mhIL-15 for treating autoimmune disorders involving an uncontrolled overproduction of IL-15.

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HIV mRNA Vaccines—Progress and Future Paths

Vaccines ◽

10.3390/vaccines9020134 ◽

2021 ◽

Vol 9 (2) ◽

pp. 134

Author(s):

Zekun Mu ◽

Barton F. Haynes ◽

Derek W. Cain

Keyword(s):

T Cell ◽

Neutralizing Antibodies ◽

Vaccination Strategy ◽

T Cell Responses ◽

Neutralizing Antibody ◽

Cytotoxic T Cell ◽

Therapeutic Vaccines ◽

Cell Responses ◽

Broadly Neutralizing Antibody ◽

Cytotoxic T Cell Responses

The SARS-CoV-2 pandemic introduced the world to a new type of vaccine based on mRNA encapsulated in lipid nanoparticles (LNPs). Instead of delivering antigenic proteins directly, an mRNA-based vaccine relies on the host’s cells to manufacture protein immunogens which, in turn, are targets for antibody and cytotoxic T cell responses. mRNA-based vaccines have been the subject of research for over three decades as a platform to protect against or treat a variety of cancers, amyloidosis and infectious diseases. In this review, we discuss mRNA-based approaches for the generation of prophylactic and therapeutic vaccines to HIV. We examine the special immunological hurdles for a vaccine to elicit broadly neutralizing antibodies and effective T cell responses to HIV. Lastly, we outline an mRNA-based HIV vaccination strategy based on the immunobiology of broadly neutralizing antibody development.

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Monoclonal antibody to SV40 T-antigen blocks lysis of cloned cytotoxic T-cell line specific for SV40 TASA

Virology ◽

10.1016/0042-6822(83)90058-2 ◽

1983 ◽

Vol 125 (1) ◽

pp. 1-7 ◽

Cited By ~ 33

Author(s):

Suelhua Pan ◽

Barbara B. Knowles

Keyword(s):

Monoclonal Antibody ◽

T Cell ◽

Cell Line ◽

T Antigen ◽

Cytotoxic T Cell ◽

Sv40 T Antigen

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Durability of Response to a Third BNT162b2 Vaccine in Adults ≥60 Years

10.1101/2021.12.25.21268336 ◽

2021 ◽

Author(s):

Noa Eliakim Raz ◽

Amos Stemmer ◽

Yaara Leibovici-Weissman ◽

Asaf Ness ◽

Muhammad Awwad ◽

...

Keyword(s):

Adverse Events ◽

Neutralizing Antibodies ◽

Multivariable Analysis ◽

Vaccine Dose ◽

Neutralizing Antibody ◽

Clinical Frailty Scale ◽

Younger Adults ◽

The Third ◽

Antibody Titers ◽

Level 2

BACKGROUND Age and frailty are strong predictors of COVID-19 mortality. After the second BNT162b2 dose, immunity wanes faster in older (≥65 years) versus younger adults. The durability of response after the third vaccine is unclear. METHODS This prospective cohort study included healthcare workers/family members ≥60 years who received a third BNT162b2 dose. Blood samples were drawn immediately before (T0), 10-19 (T1), and 74-103 (T2) days after the third dose. Antispike IgG titers were determined using a commercial assay, seropositivity was defined as ≥50 AU/mL. Neutralizing antibody titers were determined at T2. Adverse events, COVID-19 infections, and clinical frailty scale (CFS) levels were documented. RESULTS The analysis included 97 participants (median age, 70 years [IQR, 66-74], 61% women, 58% CFS level 2). IgG titers, which increased significantly from T0 to T1 (medians, 440 AU/mL [IQR, 294-923] and 25,429 [14,203-36,114] AU/mL, respectively; P<0.001), decreased significantly by T2, but all remained seropositive (median, 8,306 AU/mL [IQR, 4595-14,701], P<0.001 vs T1). In a multivariable analysis, only time from the first vaccine was significantly associated with lower IgG levels at T2 (P=0.004). At T2, 60 patients were evaluated for neutralizing antibodies; all were seropositive (median, 1,294 antibody titer [IQR, 848-2,072]). Neutralizing antibody and antispike IgG levels were correlated (R=0.6, P<0.001). No major adverse events or COVID-19 infections were reported. CONCLUSIONS Antispike IgG and neutralizing antibodies levels remain adequate 3 months after the third BNT162b2 vaccine in healthy adults ≥60 years, although the decline in IgG is concerning. A third vaccine dose in this population should be top priority.

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Adoptive therapy of canine metastatic mammary carcinoma with the human MHC non-restricted cytotoxic T-cell line TALL-104.

Oncology Reports ◽

10.3892/or.6.6.1181 ◽

1999 ◽

Cited By ~ 1

Author(s):

S Visonneau ◽

A Cesano ◽

K A Jeglum ◽

D Santoli

Keyword(s):

T Cell ◽

Cell Line ◽

Mammary Carcinoma ◽

Cytotoxic T Cell ◽

Adoptive Therapy

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A New Guaiane-type Sesquiterpenoid from a Bornean Soft Coral, Xenia stellifera

Natural Product Communications ◽

10.1177/1934578x1801300105 ◽

2018 ◽

Vol 13 (1) ◽

pp. 1934578X1801300 ◽

Cited By ~ 2

Author(s):

Chin-Soon Phan ◽

Takashi Kamada ◽

Takahiro Ishii ◽

Toshiyuki Hamada ◽

Charles Santhanaraju Vairappan

Keyword(s):

Biological Activity ◽

T Cell ◽

Cell Line ◽

Spectroscopic Data ◽

Soft Coral ◽

Leukemia Cell ◽

Leukemia Cell Line ◽

T Cell Leukemia ◽

Cell Leukemia ◽

Adult T Cell Leukemia

A new guaiane-type sesquiterpenoid, 10β- O-methyl-1αH,5αH-guaia-6-en-4β-ol (1) along with two known compounds, 10- O -methyl alismoxide (2) and alismoxide (3) were isolated from a population of Bornean soft coral Xenia stellifera. The structure of this metabolite was elucidated based on spectroscopic data such as NMR and HRESIMS. These compounds were evaluated for their biological activity against adult T-cell leukemia cell line.

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