Antibody persistence and T-cell balance: Two key factors confronting HIV vaccine development

Abstract A safe and efficacious preventive HIV vaccine, as part of a comprehensive prevention program, remains among the highest public health priorities. It would be the best tool that could reduce the spread of HIV significantly in the long run. Current AIDS vaccine candidates are unable to induce neutralizing antibodies against primary HIV isolates or only to a very limited and narrow extent, representing a major obstacle in the development of an efficacious HIV vaccine. Clinical efforts have mainly focused on T-cell vaccines such as DNA and various recombinant vectors alone or in prime-boost regimens. The Merck Ad5 vaccine not only failed to show efficacy but also was associated with increased risk of HIV acquisition in vaccinees in a Phase IIb trial. While gp120 alone was not efficacious, the ALVAC prime and gp120 boost regimen showed 31% efficacy in a Phase III trial in Thailand. These contrasting results illustrate the limitations of available laboratory assays to assess the vaccine-induced immune responses and the lack of understanding of immune correlates of protection. Efforts should therefore focus on developing vaccine candidates inducing broadly neutralizing antibodies. Similarly, new vector strategies such as replicating vectors should be explored to induce strong and broad T-cell responses in the systemic and mucosal compartments. Innovation in immune assay development and testing algorithms is critically needed. The standardization of more relevant and predictive non-human primate models for immunogenicity and efficacy studies will contribute to better and faster vaccine assessment. HIV vaccine development requires innovative ideas and a sustained long-term commitment of the scientific community, civil society, politicians, and donors and participants for clinical research.

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Faculty Opinions recommendation of New approaches to HIV vaccine development.

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

10.3410/f.725546301.793518516 ◽

2016 ◽

Author(s):

Barry Rouse

Keyword(s):

Vaccine Development ◽

Hiv Vaccine ◽

New Approaches

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Dissecting the Mechanism of T Cell Tolerance for More Effective Breast Cancer Vaccine Development

10.21236/ada435335 ◽

2004 ◽

Author(s):

Brian H. Ladle ◽

Elizabeth M. Jaffee

Keyword(s):

Breast Cancer ◽

T Cell ◽

Cancer Vaccine ◽

Vaccine Development ◽

T Cell Tolerance ◽

Cell Tolerance ◽

Breast Cancer Vaccine

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T-cell Epitope-based Vaccine Design for Nipah Virus by Reverse Vaccinology Approach

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207323666200427114343 ◽

2020 ◽

Vol 23 (8) ◽

pp. 788-796

Author(s):

Praveen K.P. Krishnamoorthy ◽

Sekar Subasree ◽

Udhayachandran Arthi ◽

Mohammad Mobashir ◽

Chirag Gowda ◽

...

Keyword(s):

T Cell ◽

Mhc Class Ii ◽

Vaccine Development ◽

Nipah Virus ◽

3D Structure ◽

Cell Epitope ◽

Class Ii ◽

Class I ◽

Reverse Vaccinology ◽

Stable Complex

Aim and Objective: Nipah virus (NiV) is a zoonotic virus of the paramyxovirus family that sporadically breaks out from livestock and spreads in humans through breathing resulting in an indication of encephalitis syndrome. In the current study, T cell epitopes with the NiV W protein antigens were predicted. Materials and Methods: Modelling of unavailable 3D structure of W protein followed by docking studies of respective Human MHC - class I and MHC - class II alleles predicted was carried out for the highest binding rates. In the computational analysis, epitopes were assessed for immunogenicity, conservation, and toxicity analysis. T – cell-based vaccine development against NiV was screened for eight epitopes of Indian - Asian origin. Results: Two epitopes, SPVIAEHYY and LVNDGLNII, have been screened and selected for further docking study based on toxicity and conservancy analyses. These epitopes showed a significant score of -1.19 kcal/mol and 0.15 kcal/mol with HLA- B*35:03 and HLA- DRB1 * 07:03, respectively by using allele - Class I and Class II from AutoDock. These two peptides predicted by the reverse vaccinology approach are likely to induce immune response mediated by T – cells. Conclusion: Simulation using GROMACS has revealed that LVNDGLNII epitope forms a more stable complex with HLA molecule and will be useful in developing the epitope-based Nipah virus vaccine.

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Use of T Cell Epitopes for Vaccine Development

Current Drug Targets - Infectious Disorders ◽

10.2174/1568005014605955 ◽

2001 ◽

Vol 1 (3) ◽

pp. 303-313 ◽

Cited By ~ 17

Author(s):

H. Sbai ◽

A. Mehta ◽

A. DeGroot

Keyword(s):

T Cell ◽

Vaccine Development ◽

T Cell Epitopes

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Computational Analysis of African Swine Fever Virus Protein Space for the Design of an Epitope-Based Vaccine Ensemble

Pathogens ◽

10.3390/pathogens9121078 ◽

2020 ◽

Vol 9 (12) ◽

pp. 1078 ◽

Cited By ~ 1

Author(s):

Albert Ros-Lucas ◽

Florencia Correa-Fiz ◽

Laia Bosch-Camós ◽

Fernando Rodriguez ◽

Julio Alonso-Padilla

Keyword(s):

T Cell ◽

Vaccine Development ◽

De Novo ◽

African Swine Fever Virus ◽

African Swine Fever ◽

Fever Virus ◽

Economic Losses ◽

Virus Protein ◽

Hemorrhagic Disease ◽

Starting Point

African swine fever virus is the etiological agent of African swine fever, a transmissible severe hemorrhagic disease that affects pigs, causing massive economic losses. There is neither a treatment nor a vaccine available, and the only method to control its spread is by extensive culling of pigs. So far, classical vaccine development approaches have not yielded sufficiently good results in terms of concomitant safety and efficacy. Nowadays, thanks to advances in genomic and proteomic techniques, a reverse vaccinology strategy can be explored to design alternative vaccine formulations. In this study, ASFV protein sequences were analyzed using an in-house pipeline based on publicly available immunoinformatic tools to identify epitopes of interest for a prospective vaccine ensemble. These included experimentally validated sequences from the Immune Epitope Database, as well as de novo predicted sequences. Experimentally validated and predicted epitopes were prioritized following a series of criteria that included evolutionary conservation, presence in the virulent and currently circulating variant Georgia 2007/1, and lack of identity to either the pig proteome or putative proteins from pig gut microbiota. Following this strategy, 29 B-cell, 14 CD4+ T-cell and 6 CD8+ T-cell epitopes were selected, which represent a starting point to investigating the protective capacity of ASFV epitope-based vaccines.

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Evolution of immune responses to SARS-CoV-2 in mild-moderate COVID-19

Nature Communications ◽

10.1038/s41467-021-21444-5 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Adam K. Wheatley ◽

Jennifer A. Juno ◽

Jing J. Wang ◽

Kevin J. Selva ◽

Arnold Reynaldi ◽

...

Keyword(s):

T Cell ◽

B Cell ◽

Vaccine Development ◽

Natural Infection ◽

Population Level ◽

Cell Dynamics ◽

Follicular Helper ◽

Cell Immunity ◽

Specific Igg ◽

Over Time

AbstractThe durability of infection-induced SARS-CoV-2 immunity has major implications for reinfection and vaccine development. Here, we show a comprehensive profile of antibody, B cell and T cell dynamics over time in a cohort of patients who have recovered from mild-moderate COVID-19. Binding and neutralising antibody responses, together with individual serum clonotypes, decay over the first 4 months post-infection. A similar decline in Spike-specific CD4+ and circulating T follicular helper frequencies occurs. By contrast, S-specific IgG+ memory B cells consistently accumulate over time, eventually comprising a substantial fraction of circulating the memory B cell pool. Modelling of the concomitant immune kinetics predicts maintenance of serological neutralising activity above a titre of 1:40 in 50% of convalescent participants to 74 days, although there is probably additive protection from B cell and T cell immunity. This study indicates that SARS-CoV-2 immunity after infection might be transiently protective at a population level. Therefore, SARS-CoV-2 vaccines might require greater immunogenicity and durability than natural infection to drive long-term protection.

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CD4 T Cell Antigens from Staphylococcus aureus Newman Strain Identified following Immunization with Heat-Killed Bacteria

Clinical and Vaccine Immunology ◽

10.1128/cvi.05642-11 ◽

2012 ◽

Vol 19 (4) ◽

pp. 477-489 ◽

Cited By ~ 9

Author(s):

Paulraj K. Lawrence ◽

Bachra Rokbi ◽

Nadège Arnaud-Barbe ◽

Eric L. Sutten ◽

Junzo Norimine ◽

...

Keyword(s):

Staphylococcus Aureus ◽

T Cell ◽

Reverse Genetics ◽

Vaccine Development ◽

Protein A ◽

Cd4 T Cell ◽

Content Type ◽

Intramammary Infections ◽

T Cell Antigens ◽

Ifn Γ

ABSTRACTStaphylococcus aureusis a commensal bacterium associated with the skin and mucosal surfaces of humans and animals that can also cause chronic infection. The emergence of antibiotic-resistant strains such as methicillin-resistantS. aureus(MRSA) and strains causing chronic intramammary infections (IMI) in cows results in severe human and livestock infections. Conventional approaches to vaccine development have yielded only a few noneffective vaccines against MRSA or IMI strains, so there is a need for improved vaccine development. CD4 T lymphocytes are required for promoting gamma interferon (IFN-γ) mediated immunoglobulin isotype switching in B lymphocytes to produce high-affinity IgG antibodies and IFN-γ-mediated phagocyte activation for an effective resolution of bacterial infection. However, the lack of known CD4 T cell antigens fromS. aureushas made it difficult to design effective vaccines. The goal of this study was to identifyS. aureusproteins recognized by immune CD4 T cells. Using a reverse genetics approach, 43 antigens were selected from theS. aureusNewman strain. These included lipoproteins, proteases, transcription regulators, an alkaline shock protein, conserved-domain proteins, hemolysins, fibrinogen-binding protein, staphylokinase, exotoxin, enterotoxin, sortase, and protein A. Screening of expressed proteins for recall T cell responses in outbred, immune calves identified 13 proteins that share over 80% sequence identity among MRSA or IMI strains. These may be useful for inclusion in a broadly protective multiantigen vaccine against MRSA or IMI.

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