Durable CD8 T Cell Memory against SARS-CoV-2 by Prime/Boost and Multi-Dose Vaccination: Considerations on Inter-Dose Time Intervals

Natalini, Ambra; Simonetti, Sonia; Sher, Carmel; D’Oro, Ugo; Hayday, Adrian; Rosa, Francesca Di

doi:10.3390/ijms232214367

Cited by 7 publications

(5 citation statements)

References 111 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nevertheless, there is no clear protocol for how best to induce long-lasting immunity in a predictable manner in respect to vaccine dose and route of administration. Similarly, even though it has been suggested that delaying vaccine boost can be beneficial for improved CD8 T cell response, at least to adenoviral vector-based vaccines, there is no current agreement on the criteria for setting the appropriate time intervals between repeated injections ( 8 – 10 ). Solving these issues can be extremely beneficial for immunological understanding and for public health policy, as emphasized by the current COVID-19 pandemic ( 11 – 13 ).…”

Section: Introductionmentioning

confidence: 99%

Improved memory CD8 T cell response to delayed vaccine boost is associated with a distinct molecular signature

et al. 2023

Self Cite

View full text Add to dashboard Cite

Effective secondary response to antigen is a hallmark of immunological memory. However, the extent of memory CD8 T cell response to secondary boost varies at different times after a primary response. Considering the central role of memory CD8 T cells in long-lived protection against viral infections and tumors, a better understanding of the molecular mechanisms underlying the changing responsiveness of these cells to antigenic challenge would be beneficial. We examined here primed CD8 T cell response to boost in a BALB/c mouse model of intramuscular vaccination by priming with HIV-1 gag-encoding Chimpanzee adenovector, and boosting with HIV-1 gag-encoding Modified Vaccinia virus Ankara. We found that boost was more effective at day(d)100 than at d30 post-prime, as evaluated at d45 post-boost by multi-lymphoid organ assessment of gag-specific CD8 T cell frequency, CD62L-expression (as a guide to memory status) and in vivo killing. RNA-sequencing of splenic gag-primed CD8 T cells at d100 revealed a quiescent, but highly responsive signature, that trended toward a central memory (CD62L+) phenotype. Interestingly, gag-specific CD8 T cell frequency selectively diminished in the blood at d100, relative to the spleen, lymph nodes and bone marrow. These results open the possibility to modify prime/boost intervals to achieve an improved memory CD8 T cell secondary response.

show abstract

Section: Introductionmentioning

confidence: 99%

Improved memory CD8 T cell response to delayed vaccine boost is associated with a distinct molecular signature

et al. 2023

Self Cite

View full text Add to dashboard Cite

show abstract

“…Knowledge of the differentiation stages of the different T cell subsets is essential to know the situation of activity and reserve that the immune system has in relation to these cells [10]. The study of the different states of activation and memory of T cells have been the subject of review [21][22][23]. Specific CD4 + T central memory (TCM), CD4 + effector memory (TEM), CD8 + TEM, and CD8 + terminal effector (TE) cells were all detectable and functional up to 12 months after the second dose of COVID-19 vaccines [24].…”

Section: Discussionmentioning

confidence: 99%

Low Number of Baselines γδ T Cells Increase the Risk of SARS-CoV-2 Post-Vaccination Infection

Andreu-Ballester,

Galindo-Regal,

Cuellar

et al. 2024

Preprint

View full text Add to dashboard Cite

Background: The effectiveness of the anti-COVID-19 vaccine remains a matter to be clarified. Methods: The humoral and cellular immunity after the administration of three doses of the Pfizer–BioNTech and Oxford AstraZeneca vaccines against SARS-CoV-2 over one year and the appearance of post-vaccination COVID-19 have been studied. Results: Anti-SARS-CoV-2 IgG and IgA antibodies showed a progressive increase throughout the vaccination period. This increase was greatest after the third dose. The highest levels were observed in subjects who had anti-SARS-CoV-2 antibodies prior to vaccination. There was an increase in CD4+ αβ, CD8+ γδ and TEM CD8+ γδ T cells, and a decrease in apoptosis in CD4+CD8+ and CD56+ αβ and γδ T cells. Post-vaccination SARS-CoV-2 infection was greater than 60%. The symptoms of COVID-19 were very mild and were related to γδ T cell deficit, specifically CD8+ TEMRA and CD56+ γδ TEM, as well as lower pre-vaccine apoptosis levels. Conclusions: Those results demonstrate the important role that γδ T cells play in SARS-CoV-2 vaccine immunization.

show abstract

“…Both vectors are considered stable, safe, and easy to produce. Besides to improve the immunostimulatory capacity of DNA plasmid used as prime, the MVA vector presents a precise expression control of the target gene and, as booster, promotes strong induction of cellular and humoral responses, in addition MVA vectored vaccines is proven to be safe in humans [ 34 – 38 ].…”

Section: Discussionmentioning

confidence: 99%

Preclinical assessment of an anti-HTLV-1 heterologous DNA/MVA vaccine protocol expressing a multiepitope HBZ protein

Daian e Silva,

Cox,

Rocha

et al. 2023

Virol J

View full text Add to dashboard Cite

Background Human T-lymphotropic virus 1 (HTLV-1) is associated with the development of several pathologies and chronic infection in humans. The inefficiency of the available treatments and the challenge in developing a protective vaccine highlight the need to produce effective immunotherapeutic tools. The HTLV-1 basic leucine zipper (bZIP) factor (HBZ) plays an important role in the HTLV-1 persistence, conferring a survival advantage to infected cells by reducing the HTLV-1 proteins expression, allowing infected cells to evade immune surveillance, and enhancing cell proliferation leading to increased proviral load. Methods We have generated a recombinant Modified Virus Vaccinia Ankara (MVA-HBZ) and a plasmid DNA (pcDNA3.1(+)-HBZ) expressing a multiepitope protein based on peptides of HBZ to study the immunogenic potential of this viral-derived protein in BALB/c mice model. Mice were immunized in a prime-boost heterologous protocol and their splenocytes (T CD4+ and T CD8+) were immunophenotyped by flow cytometry and the humoral response was evaluated by ELISA using HBZ protein produced in prokaryotic vector as antigen. Results T CD4+ and T CD8+ lymphocytes cells stimulated by HBZ-peptides (HBZ42–50 and HBZ157–176) showed polyfunctional double positive responses for TNF-α/IFN-γ, and TNF-α/IL-2. Moreover, T CD8+ cells presented a tendency in the activation of effector memory cells producing granzyme B (CD44+High/CD62L−Low), and the activation of Cytotoxic T Lymphocytes (CTLs) and cytotoxic responses in immunized mice were inferred through the production of granzyme B by effector memory T cells and the expression of CD107a by CD8+ T cells. The overall data is consistent with a directive and effector recall response, which may be able to operate actively in the elimination of HTLV-1-infected cells and, consequently, in the reduction of the proviral load. Sera from immunized mice, differently from those of control animals, showed IgG-anti-HBZ production by ELISA. Conclusions Our results highlight the potential of the HBZ multiepitope protein expressed from plasmid DNA and a poxviral vector as candidates for therapeutic vaccine.

show abstract

Durable CD8 T Cell Memory against SARS-CoV-2 by Prime/Boost and Multi-Dose Vaccination: Considerations on Inter-Dose Time Intervals

Cited by 7 publications

References 111 publications

Improved memory CD8 T cell response to delayed vaccine boost is associated with a distinct molecular signature

Improved memory CD8 T cell response to delayed vaccine boost is associated with a distinct molecular signature

Low Number of Baselines γδ T Cells Increase the Risk of SARS-CoV-2 Post-Vaccination Infection

Preclinical assessment of an anti-HTLV-1 heterologous DNA/MVA vaccine protocol expressing a multiepitope HBZ protein

Contact Info

Product

Resources

About