Protective efficacy of multiple vaccine platforms against Zika virus challenge in rhesus monkeys

ABSTRACT Rare serotype and chimeric recombinant adenovirus (rAd) vectors that evade anti-Ad5 immunity are currently being evaluated as potential vaccine vectors for human immunodeficiency virus type 1 and other pathogens. We have recently reported that a heterologous rAd prime-boost regimen expressing simian immunodeficiency virus (SIV) Gag afforded durable partial immune control of an SIV challenge in rhesus monkeys. However, single-shot immunization may ultimately be preferable for global vaccine delivery. We therefore evaluated the immunogenicity and protective efficacy of a single immunization of chimeric rAd5 hexon hypervariable region 48 (rAd5HVR48) vectors expressing SIV Gag, Pol, Nef, and Env against a homologous SIV challenge in rhesus monkeys. Inclusion of Env resulted in improved control of peak and set point SIV RNA levels following challenge. In contrast, DNA vaccine priming did not further improve the protective efficacy of rAd5HVR48 vectors in this system.

Download Full-text

Faculty Opinions recommendation of Protective efficacy of a single immunization of a chimeric adenovirus vector-based vaccine against simian immunodeficiency virus challenge in rhesus monkeys.

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

10.3410/f.1163529.625268 ◽

2009 ◽

Author(s):

Marta Marthas

Keyword(s):

Simian Immunodeficiency Virus ◽

Rhesus Monkeys ◽

Protective Efficacy ◽

Adenovirus Vector ◽

Virus Challenge ◽

Immunodeficiency Virus ◽

Simian Immunodeficiency Virus Challenge

Download Full-text

Passive immunisation of convalescent human anti-Zika plasma protects against challenge with New World Zika virus in cynomolgus macaques

npj Vaccines ◽

10.1038/s41541-020-00234-y ◽

2020 ◽

Vol 5 (1) ◽

Author(s):

Neil Berry ◽

Sarah Kempster ◽

Claire Ham ◽

Adrian Jenkins ◽

Jo Hall ◽

...

Keyword(s):

Zika Virus ◽

Vaccine Development ◽

De Novo ◽

Protective Efficacy ◽

Lymphoid Tissues ◽

Passive Immunisation ◽

Post Challenge ◽

Virus Challenge ◽

Immune Correlates ◽

Cynomolgus Macaques

Abstract Zika virus (ZIKV) causes neurological complications in susceptible individuals, highlighted in the recent South American epidemic. Natural ZIKV infection elicits host responses capable of preventing subsequent re-infection, raising expectations for effective vaccination. Defining protective immune correlates will inform viral intervention strategies, particularly vaccine development. Non-human primate (NHP) species are susceptible to ZIKV and represent models for vaccine development. The protective efficacy of a human anti-ZIKV convalescent plasma pool (16/320-14) developed as a candidate reference material for a WHO International Standard was evaluated in macaques. Convalescent plasma administered to four cynomolgus macaques (Macaca fascicularis) intra-peritoneally 24 hrs prior to sub-cutaneous challenge with 103 pfu ZIKVPRVABC59 protected against detectable infection, with absence of detectable ZIKV RNA in blood and lymphoid tissues. Passively immunised anti-ZIKV immunoglobulin administered prior to time of challenge remained present only at very low levels 42 days post-challenge. Absence of de novo antibody responses in passively immunised macaques indicate sterilising immunity compared with naïve challenge controls that exhibited active ZIKV-specific IgM and IgG responses post-challenge. Demonstration that the presence of convalescent anti-ZIKV at levels of 400 IU/mL neutralising antibody protects against virus challenge provides a scientific framework for development of anti-ZIKV vaccines and facilitates regulatory approval.

Download Full-text

Faculty Opinions recommendation of Effector memory T cell responses are associated with protection of rhesus monkeys from mucosal simian immunodeficiency virus challenge.

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

10.3410/f.1157155.621340 ◽

2009 ◽

Author(s):

Sarah Rowland-Jones

Keyword(s):

T Cell ◽

Simian Immunodeficiency Virus ◽

Rhesus Monkeys ◽

T Cell Responses ◽

Effector Memory ◽

Virus Challenge ◽

Memory T Cell ◽

Cell Responses ◽

Immunodeficiency Virus ◽

Simian Immunodeficiency Virus Challenge

Download Full-text

Cell Culture-Derived Tilapia Lake Virus-Inactivated Vaccine Containing Montanide Adjuvant Provides High Protection against Viral Challenge for Tilapia

Vaccines ◽

10.3390/vaccines9020086 ◽

2021 ◽

Vol 9 (2) ◽

pp. 86

Author(s):

Weiwei Zeng ◽

Yingying Wang ◽

Huzi Hu ◽

Qing Wang ◽

Sven M. Bergmann ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Protective Efficacy ◽

Interferon Γ ◽

Economic Losses ◽

Mrna Levels ◽

Infectious Dose ◽

Booster Immunization ◽

Virus Challenge ◽

High Level ◽

Factor Α

Tilapia lake virus (TiLV) is a newly emerging pathogen responsible for high mortality and economic losses in the global tilapia industry. Currently, no antiviral therapy or vaccines are available for the control of this disease. The goal of the present study was to evaluate the immunological effects and protective efficacy of formaldehyde- and β-propiolactone-inactivated vaccines against TiLV in the presence and absence of the Montanide IMS 1312 VG adjuvant in tilapia. We found that β-propiolactone inactivation of viral particles generated a vaccine with a higher protection efficacy against virus challenge than did formaldehyde. The relative percent survivals of vaccinated fish at doses of 108, 107, and 106 50% tissue culture infectious dose (TCID50)/mL were 42.9%, 28.5%, and 14.3% in the absence of the adjuvant and 85.7%, 64.3%, and 32.1% in its presence, respectively. The vaccine generated specific IgM and neutralizing antibodies against TiLV at 3 weeks following immunization that were significantly increased after a second booster immunization. The steady state mRNA levels of the genes tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interferon γ (IFN-γ), cluster of differentiation 4 (CD4), major histocompatibility complex (MHC)-Ia, and MHC-II were all increased and indicated successful immune stimulation against TiLV. The vaccine also significantly lowered the viral loads and resulted in significant increases in survival, indicating that the vaccine may also inhibit viral proliferation as well as stimulate a protective antibody response. The β-propiolactone-inactivated TiLV vaccine coupled with the adjuvant Montanide IMS 1312 VG and booster immunizations can provide a high level of protection from virus challenge in tilapia.

Download Full-text

Assessment of immunogenicity and protective efficacy of ZyCoV-D DNA vaccine candidates in Rhesus macaques against SARS-CoV-2 infection

10.1101/2021.02.02.429480 ◽

2021 ◽

Author(s):

Pragya D Yadav ◽

Sanjay Kumar ◽

Kshitij Agarwal ◽

Mukul Jain ◽

Dilip R Patil ◽

...

Keyword(s):

Vaccine Candidate ◽

Protective Efficacy ◽

Rhesus Macaques ◽

Herd Immunity ◽

Lavage Fluid ◽

Injection System ◽

Protective Measure ◽

Vaccine Candidates ◽

Virus Challenge ◽

Syringe Needle

AbstractVaccines remain the key protective measure to achieve herd immunity to control the disease burden and stop COVID-19 pandemic. We have developed and assessed the immunogenicity and protective efficacy of two formulations (1mg and 2mg) of ZyCoV-D (a plasmid DNA based vaccine candidates) administered through Needle Free Injection System (NFIS) and syringe-needle (intradermal) in rhesus macaques with three dose vaccine regimens. The vaccine candidate 2mg dose administered using Needle Free Injection System (NFIS) elicited a significant immune response with development of SARS-CoV-2 S1 spike region specific IgG and neutralizing antibody (NAb) titers during the immunization phase and significant enhancement in the levels after the virus challenge. In 2 mg NFIS group the IgG and NAb titers were maintained and showed gradual rise during the immunization period (15 weeks) and till 2 weeks after the virus challenge. It also conferred better protection to macaques evident by the viral clearance from nasal swab, throat swab and bronchoalveolar lavage fluid specimens in comparison with macaques from other immunized groups. In contrast, the animals from placebo group developed high levels of viremia and lung disease following the virus challenge. Besides this, the vaccine candidate also induced increase lymphocyte proliferation and cytokines response (IL-6, IL-5).The administration of the vaccine candidate with NFIS generated a better immunogenicity response in comparison to syringe-needle (intradermal route). The study demonstrated immunogenicity and protective efficacy of the vaccine candidate, ZyCoV-D in rhesus macaques.

Download Full-text

Zika Virus Persistence in the Central Nervous System and Lymph Nodes of Rhesus Monkeys

Cell ◽

10.1016/j.cell.2017.04.008 ◽

2017 ◽

Vol 169 (4) ◽

pp. 610-620.e14 ◽

Cited By ~ 127

Author(s):

Malika Aid ◽

Peter Abbink ◽

Rafael A. Larocca ◽

Michael Boyd ◽

Ramya Nityanandam ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Lymph Nodes ◽

Zika Virus ◽

Rhesus Monkeys ◽

Virus Persistence ◽

The Central Nervous System

Download Full-text

Vi capsular polysaccharide-protein conjugates for prevention of typhoid fever. Preparation, characterization, and immunogenicity in laboratory animals.

Journal of Experimental Medicine ◽

10.1084/jem.166.5.1510 ◽

1987 ◽

Vol 166 (5) ◽

pp. 1510-1524 ◽

Cited By ~ 81

Author(s):

S C Szu ◽

A L Stone ◽

J D Robbins ◽

R Schneerson ◽

J B Robbins

Keyword(s):

Typhoid Fever ◽

Rhesus Monkeys ◽

Capsular Polysaccharide ◽

Protective Antigen ◽

Protective Efficacy ◽

Protective Action ◽

The United States ◽

Laboratory Animals ◽

Protein Conjugates ◽

High Yields

The Vi has proven to be a protective antigen in two double masked, controlled clinical trials in areas with high rates of typhoid fever (approximately 1% per annum). In both studies the protective efficacy of the Vi was approximately 70%. Approximately 75% of subjects in these areas responded with a fourfold or greater rise of serum Vi antibodies. In contrast, the Vi elicited a fourfold or greater rise in 95-100% of young adults in France and the United States. Methods were devised, therefore, to synthesize Vi-protein conjugates in order to both enhance the antibody response and confer T-dependent properties to the Vi (and theoretically increase its protective action in populations at high risk for typhoid fever). We settled on a method that used the heterobifunctional crosslinking reagent, N-succinimidyl-3-(2-pyridyldithio)-propionate (SPDP), to bind thiol derivatives of the Vi to proteins. This synthetic scheme was reproducible, provided high yields of Vi-protein conjugates, and was applicable to several medically relevant proteins such as diphtheria and tetanus toxoids. The resultant conjugates were more immunogenic in mice and juvenile Rhesus monkeys than the Vi alone. In contrast to the T-independent properties of the Vi, conjugates of this polysaccharide with several medically relevant proteins induced booster responses in mice and in juvenile Rhesus monkeys. Clinical studies with Vi-protein conjugates are planned. This scheme is also applicable to synthesize protein conjugates with other polysaccharides that have carboxyl functions.

Download Full-text