Development of Th1 Imprints to rBCG Expressing a Foreign Protein: Implications for Vaccination against HIV-1 and Diverse Influenza Strains

We demonstrate here that immunizing naïve mice with low numbers of recombinant Bacille Calmette-Guérin (rBCG) expressingβ-galactosidase (β-gal) generates predominant Th1 responses to both BCG andβ-gal whereas infection with high numbers generates a mixed Th1/Th2 response to both BCG andβ-gal. Furthermore, the Th1 response to both BCG andβ-gal is stable when mice, pre-exposed to low numbers of rBCG, are challenged four months later with high numbers of rBCG. Thus the Th1/Th2 phenotypes of the immune responses toβ-gal and to BCG are “coherently” regulated. Such rBCG vectors, encoding antigens of pathogens preferentially susceptible to cell-mediated attack, may be useful in vaccinating against such pathogens. We discuss vaccination strategies employing rBCG vectors that are designed to provide protection against diverse influenza strains or numerous variants of HIV-1 and consider what further experiments are essential to explore the possibility of realizing such strategies.

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Mycobacterial Dose Defines the Th1/Th2 Nature of the Immune Response Independently of Whether Immunization Is Administered by the Intravenous, Subcutaneous, or Intradermal Route

Infection and Immunity ◽

10.1128/iai.66.12.5743-5750.1998 ◽

1998 ◽

Vol 66 (12) ◽

pp. 5743-5750 ◽

Cited By ~ 122

Author(s):

Carl A. Power ◽

Guojian Wei ◽

Peter A. Bretscher

Keyword(s):

Humoral Response ◽

Cell Mediated Immunity ◽

Low Doses ◽

Th2 Response ◽

Mixed Cell ◽

Th1 Response ◽

Vaccination Strategies ◽

Tuberculous Disease ◽

Higher Doses ◽

Intradermal Route

ABSTRACT It is believed that cell-mediated immunity alone can containMycobacterium tuberculosis, the pathogen responsible for tuberculosis. The induction of antibody, or of a mixed cell-mediated/humoral response, is associated with tuberculous disease. It is therefore important to determine the conditions of immunization with bacille Calmette Guérin (BCG), the attenuated strain of Mycobacterium bovis used to vaccinate humans against tuberculosis, that optimally induces an exclusive cell-mediated, Th1 response. Such a determination will then allow an assessment of whether the generation of such an exclusive Th1 response results in the generation of a Th1 imprint against mycobacteria. This Th1 imprint would ensure that the Th1 response is predominant following any challenge. We therefore tested the proposition that the dose of mycobacteria used for immunization generally determines the Th1/Th2 nature of the ensuing response. Our results demonstrate that relatively low doses lead to an almost exclusive cell-mediated, Th1 response, while higher doses induce a mixed Th1/Th2 response. Furthermore, the dependence on dose is independent of whether BCG is administered intravenously, subcutaneously, or intradermally. The implications of our findings to understanding how different classes of immunity are induced, to the epidemiology of tuberculosis, and to the design of effective vaccination strategies are discussed.

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Cynomolgus macaques immunized with two HIV-1 Tat stabilized proteins raise strong and long-lasting immune responses with a pattern of Th1/Th2 response differing from that in mice

Vaccine ◽

10.1016/j.vaccine.2009.06.083 ◽

2009 ◽

Vol 27 (39) ◽

pp. 5349-5356 ◽

Cited By ~ 11

Author(s):

Sabrina Turbant ◽

Frédéric Martinon ◽

Gervaise Moine ◽

Roger Le Grand ◽

Michel Léonetti

Keyword(s):

Immune Responses ◽

Th2 Response ◽

Cynomolgus Macaques ◽

Hiv 1

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Follow-up study of cellular immune responses in peripheral blood of HIV-1 infected persons in Bulgaria

Immunology Letters ◽

10.1016/s0165-2478(97)87381-6 ◽

1997 ◽

Vol 56 (1-3) ◽

pp. 136

Author(s):

R Markova

Keyword(s):

Immune Responses ◽

Peripheral Blood ◽

Cellular Immune Responses ◽

Follow Up Study ◽

Cellular Immune ◽

Hiv 1

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Faculty Opinions recommendation of Evidence of HIV-1 adaptation to HLA-restricted immune responses at a population level.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1007387.92158 ◽

2002 ◽

Author(s):

Sarah Rowland-Jones

Keyword(s):

Immune Responses ◽

Population Level ◽

Hiv 1

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Faculty Opinions recommendation of Mosaic HIV-1 vaccines expand the breadth and depth of cellular immune responses in rhesus monkeys.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.2620963.2280064 ◽

2010 ◽

Author(s):

Yufei Wang

Keyword(s):

Immune Responses ◽

Rhesus Monkeys ◽

Cellular Immune Responses ◽

Cellular Immune ◽

Hiv 1

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Faculty Opinions recommendation of Identification of effective subdominant anti-HIV-1 CD8+ T cells within entire post-infection and post-vaccination immune responses.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725369604.793506152 ◽

2015 ◽

Author(s):

Gerrit Koopman

Keyword(s):

T Cells ◽

Immune Responses ◽

Cd8 T Cells ◽

Post Infection ◽

Post Vaccination ◽

Anti Hiv ◽

Hiv 1

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Immunogenicity and protective efficacy of enterotoxigenic Escherichia coli (ETEC) total RNA against ETEC challenge in a mouse model

Scientific Reports ◽

10.1038/s41598-020-77551-8 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Mandi Liu ◽

Yue Zhang ◽

Di Zhang ◽

Yun Bai ◽

Guomei Liu ◽

...

Keyword(s):

Escherichia Coli ◽

Mouse Model ◽

Immune Responses ◽

Protective Efficacy ◽

Enterotoxigenic Escherichia Coli ◽

Economic Losses ◽

Th2 Response ◽

Total Rna ◽

Etec Infection

AbstractEnterotoxigenic Escherichia coli (ETEC), an essential cause of post-weaning diarrhea (PWD) in piglets, leads to significant economic losses to the pig industry. The present study aims to identify the role of ETEC total RNA in eliciting immune responses to protect animals against ETEC infection. The results showed that the total RNA isolated from pig-derived ETEC K88ac strain effectively stimulated the IL-1β secretion of porcine intestinal epithelial cells (IPEC-J2). The mouse model immunized with ETEC total RNA via intramuscular injection (IM) or oral route (OR) was used to evaluate the protective efficiency of the ETEC total RNA. The results suggested that 70 μg ETEC total RNA administered by either route significantly promoted the production of the serum IL-1β and K88ac specific immunoglobulins (IgG, IgM, and IgA). Besides, the ETEC RNA administration augmented strong mucosal immunity by elevating K88ac specific IgA level in the intestinal fluid. Intramuscularly administered RNA induced a Th1/Th2 shift toward a Th2 response, while the orally administered RNA did not. The ETEC total RNA efficiently protected the animals against the ETEC challenge either by itself or as an adjuvant. The histology characterization of the small intestines also suggested the ETEC RNA administration protected the small intestinal structure against the ETEC infection. Particularly of note was that the immunity level and protective efficacy caused by ETEC RNA were dose-dependent. These findings will help understand the role of bacterial RNA in eliciting immune responses, and benefit the development of RNA-based vaccines or adjuvants.

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COVID-19: Mechanisms of Vaccination and Immunity

Vaccines ◽

10.3390/vaccines8030404 ◽

2020 ◽

Vol 8 (3) ◽

pp. 404 ◽

Cited By ~ 1

Author(s):

Daniel E. Speiser ◽

Martin F. Bachmann

Keyword(s):

Immune Responses ◽

Clinical Management ◽

Neutralizing Antibodies ◽

Vaccine Development ◽

Public Life ◽

High Affinity ◽

Vaccination Strategies ◽

Detailed Evaluation ◽

Pros And Cons

Vaccines are needed to protect from SARS-CoV-2, the virus causing COVID-19. Vaccines that induce large quantities of high affinity virus-neutralizing antibodies may optimally prevent infection and avoid unfavorable effects. Vaccination trials require precise clinical management, complemented with detailed evaluation of safety and immune responses. Here, we review the pros and cons of available vaccine platforms and options to accelerate vaccine development towards the safe immunization of the world’s population against SARS-CoV-2. Favorable vaccines, used in well-designed vaccination strategies, may be critical for limiting harm and promoting trust and a long-term return to normal public life and economy.

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