Viral-vectored boosting of OmcB- or CPAF-specific T-cell responses fail to enhance protection from Chlamydia muridarum in infection-immune mice and elicits a non-protective CD8-dominant response in naïve mice DOI Creative Commons
Taylor B. Poston,

Jenna Girardi,

A Grace Polson

et al.

Mucosal Immunology, Journal Year: 2024, Volume and Issue: 17(5), P. 1005 - 1018

Published: July 3, 2024

A vaccine is needed to combat the Chlamydia epidemic. Replication-deficient viral vectors are safe and induce antigen-specific T-cell memory. We tested ability of intramuscular immunization with modified vaccinia Ankara (MVA) virus or chimpanzee adenovirus (ChAd) expressing chlamydial outer membrane protein (OmcB) secreted protein, protease-like activating factor (CPAF), enhance immunity protection in mice previously infected plasmid-deficient muridarum CM972 elicit naïve mice. MVA.OmcB MVA.CPAF increased T cells CM972-immune ∼150 50-fold, respectively, but failed improve bacterial clearance. ChAd.OmcB/MVA.OmcB prime-boost elicited a cluster differentiation (CD) 8-dominant response dominated by (CD)8 that protect. ChAd.CPAF/ChAd.CPAF also induced CD8-dominant marginal reduction burden. Challenge ChAd.CPAF-immunized genetically deficient CD4 CD8 showed was entirely CD4-dependent. CD4-deficient had prolonged infection, whereas CD8-deficient higher frequencies CPAF-specific cells, earlier clearance, reduced burden than wild-type controls. These data reinforce essential nature from genital infection need for platforms drive CD4-dominant responses.

Language: Английский

Viral vectored vaccines: design, development, preventive and therapeutic applications in human diseases DOI Creative Commons
Shen Wang, Bo Liang,

Weiqi Wang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: April 7, 2023

Abstract Human diseases, particularly infectious diseases and cancers, pose unprecedented challenges to public health security the global economy. The development distribution of novel prophylactic therapeutic vaccines are prioritized countermeasures human disease. Among all vaccine platforms, viral vector offer distinguished advantages represent prominent choices for pathogens that have hampered control efforts based on conventional approaches. Currently, remain one best strategies induction robust humoral cellular immunity against diseases. Numerous viruses different families origins, including vesicular stomatitis virus, rabies parainfluenza measles Newcastle disease influenza adenovirus poxvirus, deemed be vectors differ in structural characteristics, design strategy, antigen presentation capability, immunogenicity protective efficacy. This review summarized overall profile strategies, progress advance steps taken address barriers deployment these vaccines, simultaneously highlighting their potential mucosal delivery, application cancer as well other key aspects concerning rational vaccines. Appropriate accurate technological advances would consolidate position a leading approach accelerate breakthroughs facilitate rapid response emergencies.

Language: Английский

Citations

96
Mucosal vaccines for SARS-CoV-2: scientific gaps and opportunities—workshop report DOI Creative Commons
Jane M. Knisely, Lucas E. Buyon, Rebecca Mandt

et al.

npj Vaccines, Journal Year: 2023, Volume and Issue: 8(1)

Published: April 12, 2023

On November 7th and 8th, 2022, The National Institute of Allergy Infectious Diseases (NIAID), part the Institutes Health (NIH), Coalition for Epidemic Preparedness Innovation (CEPI), Bill & Melinda Gates Foundation (BMGF), Biomedical Advanced Research Development Authority (BARDA), Wellcome Trust hosted a virtual workshop entitled "Mucosal Vaccines SARS-CoV-2: Scientific Gaps Opportunities." During workshop, researchers vaccine developers from around world discussed potential mucosal vaccines to block SARS-CoV-2 transmission reviewed status research. Here, we summarize key challenges opportunities in basic, translational, clinical research that were highlighted during meeting. We also provide recommendations advance field accelerate development SARS-CoV-2.

Language: Английский

Citations

72
Inhaled SARS-CoV-2 vaccine for single-dose dry powder aerosol immunization DOI
Tong Ye, Zhouguang Jiao, Xin Li

et al.

Nature, Journal Year: 2023, Volume and Issue: 624(7992), P. 630 - 638

Published: Dec. 13, 2023

Language: Английский

Citations

59
Mucosal vaccines for SARS-CoV-2: triumph of hope over experience DOI Creative Commons

Devaki Pilapitiya,

Adam K. Wheatley, Hyon‐Xhi Tan

et al.

EBioMedicine, Journal Year: 2023, Volume and Issue: 92, P. 104585 - 104585

Published: May 3, 2023

Currently approved COVID-19 vaccines administered parenterally induce robust systemic humoral and cellular responses. While highly effective against severe disease, there is reduced effectiveness of these in preventing breakthrough infection and/or onward transmission, likely due to poor immunity elicited at the respiratory mucosa. As such, has been considerable interest developing novel mucosal that engenders more localised immune responses provide better protection recall site virus entry, contrast traditional vaccine approaches focus on immunity. In this review, we explore adaptive components immunity, evaluate epidemiological studies dissect if conferred by parenteral vaccination or drives differential efficacy acquisition discuss undergoing clinical trials assess key challenges prospects for development.

Language: Английский

Citations

48
Mucosal boosting enhances vaccine protection against SARS-CoV-2 in macaques DOI Creative Commons
Katherine McMahan, Frank Wegmann, Malika Aïd

et al.

Nature, Journal Year: 2023, Volume and Issue: 626(7998), P. 385 - 391

Published: Dec. 14, 2023

Abstract A limitation of current SARS-CoV-2 vaccines is that they provide minimal protection against infection with Omicron subvariants 1,2 , although still severe disease. Enhanced mucosal immunity may be required to block and onward transmission. Intranasal administration has proven inconsistent 3–7 suggesting alternative immunization strategies required. Here we show intratracheal boosting a bivalent Ad26-based vaccine results in substantial induction humoral cellular near-complete BQ.1.1 challenge. total 40 previously immunized rhesus macaques were boosted Ad26 by the intramuscular, intranasal routes, or mRNA route. route led expansion neutralizing antibodies, IgG IgA binding CD8 + CD4 T cell responses, which exceeded those induced intramuscular routes. Intratracheal also robust upregulation cytokine, natural killer, B pathways lungs. After challenge high dose BQ.1.1, provided protection, whereas other proved less effective. Protective efficacy correlated best immune responses. These data demonstrate these induce immunity, feasibility developing respiratory viral infections.

Language: Английский

Citations

47
Mucosal vaccine-induced cross-reactive CD8+ T cells protect against SARS-CoV-2 XBB.1.5 respiratory tract infection DOI Creative Commons

Baoling Ying,

Tamarand L. Darling, Pritesh Desai

et al.

Nature Immunology, Journal Year: 2024, Volume and Issue: 25(3), P. 537 - 551

Published: Feb. 9, 2024

Abstract A nasally delivered chimpanzee adenoviral-vectored severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine (ChAd-SARS-CoV-2-S) is currently used in India (iNCOVACC). Here, we update this by creating ChAd-SARS-CoV-2-BA.5-S, which encodes a prefusion-stabilized BA.5 spike protein. Whereas serum neutralizing antibody responses induced monovalent or bivalent adenoviral vaccines were poor against the antigenically distant XBB.1.5 strain and insufficient to protect passive transfer experiments, mucosal cross-reactive memory T cell robust, protection was evident WA1/2020 D614G Omicron variants BQ.1.1 mice hamsters. However, depletion of CD8 + cells before challenge resulted loss upper lower tract infection. Thus, stimulate immunity emerging SARS-CoV-2 strains, mediate lung infection strains setting low levels antibodies.

Language: Английский

Citations

17
An Update on Anti-COVID-19 Vaccines and the Challenges to Protect Against New SARS-CoV-2 Variants DOI Creative Commons
Fábio Mambelli, Ana Carolina V. S. C. de Araujo, Jéssica Pires Farias

et al.

Pathogens, Journal Year: 2025, Volume and Issue: 14(1), P. 23 - 23

Published: Jan. 1, 2025

The COVID-19 pandemic has posed a significant threat to global health systems, with extensive impacts across many sectors of society. been responsible for millions deaths worldwide since its first identification in late 2019. Several actions have taken prevent the disease, including unprecedented fast development and vaccination campaigns, which were pivotal reducing symptoms deaths. Given impact pandemic, continuous changes virus, present vaccine technologies, this review analyzes how, so far, we met challenge by emergence new variants discusses how next-generation pan-coronavirus vaccines, enhanced longevity breadth immune responses, may be tackled alternative administration routes antigen delivery platforms. By addressing these critical aspects, aims contribute ongoing efforts achieve long-term control COVID-19, stimulating discussion work on vaccines capable facing future waves infection.

Language: Английский

Citations

2
The role of vaccines in the COVID-19 pandemic: what have we learned? DOI Creative Commons
Florian Krammer

Seminars in Immunopathology, Journal Year: 2023, Volume and Issue: 45(4-6), P. 451 - 468

Published: July 12, 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged late in 2019 and caused the disease (COVID-19) pandemic that has so far claimed approximately 20 million lives. Vaccines were developed quickly, became available end of 2020, had a tremendous impact on protection from SARS-CoV-2 mortality but with emerging variants morbidity was diminished. Here I review what we learned COVID-19 vaccinologist's perspective.

Language: Английский

Citations

42
Phase III Pivotal comparative clinical trial of intranasal (iNCOVACC) and intramuscular COVID 19 vaccine (Covaxin®) DOI Creative Commons
Chandramani Singh, Savita Verma,

Prabhakar Reddy

et al.

npj Vaccines, Journal Year: 2023, Volume and Issue: 8(1)

Published: Aug. 18, 2023

One of the most preferable characteristics for a COVID-19 vaccine candidate is ability to reduce transmission and infection SARS-CoV-2, in addition disease prevention. Unlike intramuscular vaccines, intranasal vaccines may offer this by generating mucosal immunity. In open-label, randomised, multicentre, phase 3 clinical trial (CTRI/2022/02/40065; ClinicalTrials.gov: NCT05522335), healthy adults were randomised receive two doses, 28 days apart, either adenoviral vectored SARS-CoV-2 (BBV154) or licensed vaccine, Covaxin®. Between April 16 June 4, 2022, we enrolled 3160 subjects whom, 2971 received 2 doses BBV154 161 Covaxin. On Day 42, 14 after second dose, induced significant serum neutralization antibody titers against ancestral (Wuhan) virus, which met pre-defined superiority criterion over Further, both showed cross protection Omicron BA.5 variant. Salivary IgA found be higher BBV154. addition, extensive evaluation T cell immunity revealed comparable responses cohorts due prior infection. However, significantly more specific IgA-secreting plasmablasts, post vaccination, whereas Covaxin recipients plasmablasts only at day 42. Both well tolerated. Overall reported solicited reactions 6.9% 25.5% unsolicited 1.2% 3.1% Covaxin® participants respectively.

Language: Английский

Citations

41
Hybrid Immunity to SARS-CoV-2 from Infection and Vaccination—Evidence Synthesis and Implications for New COVID-19 Vaccines DOI Creative Commons
Júlia Spinardi, Amit Srivastava

Biomedicines, Journal Year: 2023, Volume and Issue: 11(2), P. 370 - 370

Published: Jan. 27, 2023

COVID-19 has taken a severe toll on the global population through infections, hospitalizations, and deaths. Elucidating SARS-CoV-2 infection-derived immunity led to development of multiple effective vaccines their implementation into mass-vaccination programs worldwide. After ~3 years, substantial proportion human possesses from infection and/or vaccination. With waning immune protection over time against emerging variants, it is essential understand duration protection, breadth coverage, effects reinfection. This targeted review summarizes available research literature infection-derived, vaccination-elicited, hybrid immunity. Infection-derived shown 93-100% outcomes for up 8 months, but reinfection observed with some virus variants. Vaccination elicits high levels neutralizing antibodies CD4+ CD8+ T-cell responses. Hybrid enables strong, broad responses, high-quality memory B cells generated at 5- 10-fold higher levels, versus or vaccination alone symptomatic disease lasting 6-8 months. evolution more transmissible immunologically divergent variants necessitated updating vaccines. To ensure continued regulators vaccine technical committees recommend variant-specific bivalent

Language: Английский

Citations

35