Zika virus (ZIKV) is a flavivirus that is responsible for the current epidemic in Brazil and the Americas. ZIKV has been causally associated with fetal microcephaly, intrauterine growth restriction, ...and other birth defects in both humans and mice. The rapid development of a safe and effective ZIKV vaccine is a global health priority, but very little is currently known about ZIKV immunology and mechanisms of immune protection. Here we show that a single immunization with a plasmid DNA vaccine or a purified inactivated virus vaccine provides complete protection in susceptible mice against challenge with a strain of ZIKV involved in the outbreak in northeast Brazil. This ZIKV strain has recently been shown to cross the placenta and to induce fetal microcephaly and other congenital malformations in mice. We produced DNA vaccines expressing ZIKV pre-membrane and envelope (prM-Env), as well as a series of deletion mutants. The prM-Env DNA vaccine, but not the deletion mutants, afforded complete protection against ZIKV, as measured by absence of detectable viraemia following challenge, and protective efficacy correlated with Env-specific antibody titers. Adoptive transfer of purified IgG from vaccinated mice conferred passive protection, and depletion of CD4 and CD8 T lymphocytes in vaccinated mice did not abrogate this protection. These data demonstrate that protection against ZIKV challenge can be achieved by single-shot subunit and inactivated virus vaccines in mice and that Env-specific antibody titers represent key immunologic correlates of protection. Our findings suggest that the development of a ZIKV vaccine for humans is likely to be achievable.
The novel betacoronavirus, SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), has spread across the globe at an unprecedented rate since its first emergence in Wuhan City, China in ...December 2019. Scientific communities around the world have been rigorously working to develop a potent vaccine to combat COVID-19 (coronavirus disease 2019), employing conventional and novel vaccine strategies. Gene-based vaccine platforms based on viral vectors, DNA, and RNA, have shown promising results encompassing both humoral and cell-mediated immune responses in previous studies, supporting their implementation for COVID-19 vaccine development. In fact, the U.S. Food and Drug Administration (FDA) recently authorized the emergency use of two RNA-based COVID-19 vaccines. We review current gene-based vaccine candidates proceeding through clinical trials, including their antigenic targets, delivery vehicles, and route of administration. Important features of previous gene-based vaccine developments against other infectious diseases are discussed in guiding the design and development of effective vaccines against COVID-19 and future derivatives.
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Ebola virus (EBOV) is a highly lethal member of the Filoviridae family associated with human hemorrhagic disease. Despite being a sporadic disease, it caused a large outbreak in 2014-2016 in West ...Africa and another outbreak recently in the Democratic Republic of Congo. Several vaccine candidates are currently in preclinical and clinical studies but none are stable without cold chain storage.
We used preservation by vaporization (PBV), a novel processing technology to heat-stabilize FiloRab1 (inactivated rabies-based Ebola vaccine), a candidate Ebola vaccine, and stored the vials at temperatures ranging from 4°C to 50°C for 10 days to 12 months. We immunized Syrian hamsters with the best long-term stable FiloRab1 PBV vaccines and challenged them with rabies virus (RABV).
Syrian hamsters immunized with FiloRab1 PBV-processed vaccines stored at temperatures of 4°C and 37°C for 6 months, and at 50°C for 2 weeks, seroconverted against both RABV-G and EBOV-GP. Notably, all of the FiloRab1 PBV vaccines proved to be 100% effective in a RABV challenge model.
We successfully demonstrated that the FiloRab1 PBV vaccines are stable and efficacious for up to 6 months when stored at temperatures ranging from 4°C to 37°C and for up to 2 weeks at 50°C.
Most pathogens access the body through the mucosal membranes. Therefore, effective vaccines that protect at these sites are much needed. However, despite early success with the live attenuated oral ...polio vaccine over 50 years ago, only a few new mucosal vaccines have been subsequently launched. This is partly due to problems with developing safe and effective mucosal adjuvants. In the past decade, however, the successful development of live attenuated mucosal vaccines against influenza virus and rotavirus infections has boosted interest in this field, and great expectations for new mucosal vaccines lie ahead. Here, I discuss the expanding knowledge and strategies used in the development of mucosal vaccines.
Coronavirus disease 2019 (COVID-19) has affected more than 96 million people worldwide, leading the World Health Organization (WHO) to declare a pandemic in March 2020. Although an optimal medical ...treatment of COVID-19 remains uncertain, an unprecedented global effort to develop an effective vaccine hopes to restore pre-pandemic conditions. Since cancer patients as a group have been shown to be at a higher risk of severe COVID-19, the development of safe and effective vaccines is crucial. However, cancer patients may be underrepresented in ongoing phase 3 randomised clinical trials investigating COVID-19 vaccines. Therefore, we encourage stakeholders to provide real-time data about the characteristics of recruited participants, including clearly identifiable subgroups, like cancer patients, with sample sizes large enough to determine safety and efficacy. Moreover, we envisage a prompt implementation of suitable registries for pharmacovigilance reporting, in order to monitor the effects of COVID-19 vaccines and immunisation rates in patients with cancer. That said, data extrapolation from other vaccine trials (e.g. anti-influenza virus) showed a favourable safety and efficacy profile for cancer patients. On the basis of the evidence discussed, we believe that the benefits of the vaccination outweigh the risks. Consequently, healthcare authorities should prioritise vaccinations for cancer patients, with the time-point of administration agreed on a case-by-case basis. In this regard, the American Society of Clinical Oncology and the European Society of Medical Oncology are advocating for cancer patients a high priority status, in the hope of attenuating the consequences of the pandemic in this particularly vulnerable population.
•COVID-19 has affected more than 96 million people. WHO declared a pandemic in March 2020.•Cancer patients as a group have been shown to be at a higher risk of severe COVID-19.•Evidence from ongoing vaccine RCTs is currently lacking for cancer patients.•Data extrapolation from other vaccines showed a favourable safety and efficacy profile.•Cancer patients need vaccination prioritisation and tailored administration time-point.
•Infants are at particular risk of meningococcal disease caused by Neisseria meningitidis.•MenACWY-TT is a meningococcal vaccine targeting 4 of the 6 most prevalent serogroups.•3+1 (at ages 2, 4, 6, ...15–18 months); 1+1 (6, 15–18 months) or 1-dose (15–18 months) MenACWY-TT schedules were immunogenic.•Co-administration of MenACWY-TT with other pediatric vaccines was well-tolerated.
Invasive meningococcal disease has a high burden in young children, particularly during infancy. We investigated the immunogenicity and safety of a quadrivalent meningococcal conjugated vaccine (MenACWY-TT) co-administered with routine vaccines in healthy infants.
In this phase IIIb study (NCT01340898) conducted in 2 centers in Lebanon and Mexico, 750 infants were randomized (2:1:1) to receive MenACWY-TT according to 3 schedules: 3+1 (at ages 2, 4, 6 and 15–18 months; group ACWY3+1); 1+1 (at 6 and 15–18 months; group ACWY1+1) or single-dose at 15–18 months (group ACWY1). All infants received PHiD-CV and DTPa-IPV/Hib at ages 2, 4, 6, 15–18 months. Immune responses to MenACWY-TT were assessed by rSBA and hSBA at 7 months (groups ACWY3+1, ACWY1+1) and pre- and post-vaccination at 15–18 months of age (all groups). Immune responses to co-administered vaccines, reactogenicity and safety were also evaluated.
Immunogenicity of MenACWY-TT at 1 month post-primary vaccination was demonstrated in group ACWY3+1: the lower limit of the 95% confidence interval for the percentage of infants with rSBA titers ≥8 was >80% for each serogroup. At 7 months of age, ≥93.9% of MenACWY-TT-primed infants had rSBA titers ≥8. Post-MenACWY-TT vaccination at age 15–18 months, ≥96.3% of participants in all groups had rSBA titers ≥8, regardless of the number of doses received previously. The percentage of infants with hSBA titers ≥4 were ≥87.2% and ≥89.7% at post-primary and booster/single-dose vaccination, respectively. Immune responses to PHiD-CV and DTPa-IPV/Hib did not seem impacted by co-administration with MenACWY-TT in infancy. The incidence of all adverse events was similar among groups. Serious adverse events were reported for 63/750 children in all groups; none were considered vaccine-related by investigators.
Primary vaccination with 3 or 1 dose(s) of MenACWY-TT when co-administered with routine pediatric vaccines in infants is immunogenic and well-tolerated.
Foot-and-mouth disease (FMD) has been a major threat to livestock across the world. The predominant method of controlling this disease in endemic regions is through regular vaccination with ...inactivated vaccine. However, there are many limitations. For instance, cultivation of virulent FMD virus (FMDV) in the manufacturing units poses a risk of escape from production sites. Vaccines may sometimes contain traces of FMD viral non-structural proteins (NSPs), therefore, interfering with the NSP-based serological differentiation infected from vaccinated animals (DIVA). Moreover, vaccines are unable to eliminate virus from carrier animals. To address the shortcomings of inactivated vaccines, many efforts are currently devoted to develop novel vaccines including attenuated and/or marker inactivated vaccines, recombinant protein vaccines, synthetic peptide vaccines, and empty capsid vaccines. Here, we review the research progress of novel vaccines, problems that remain to be solved, and also raise some suggestions that would help in the development of FMD vaccines.
Highlights • DTaP-IPV-HB-PRP-T immunogenicity is similar when given concomitantly with a meningococcal C conjugate vaccine or alone. • The safety profile of DTaP-IPV-HB-PRP-T is similar when given ...concomitantly with a meningococcal C conjugate vaccine or alone. • These data support the concomitant use of DTa-IPV-HB-PRP-T vaccine with a meningococcal C conjugate vaccine.
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Vaccination is the most effective method to prevent influenza infection. However, current influenza vaccines have several limitations. Relatively long production times, limited ...vaccine capacity, moderate efficacy in certain populations and lack of cross-reactivity are important issues that need to be addressed. We give an overview of the current status and novel developments in the landscape of influenza vaccines from an interdisciplinary point of view. The feasibility of novel vaccine concepts not only depends on immunological or clinical outcomes, but also depends on biotechnological aspects, such as formulation and production methods, which are frequently overlooked. Furthermore, the next generation of influenza vaccines is addressed, which hopefully will bring cross-reactive influenza vaccines. These developments indicate that an exciting future lies ahead in the influenza vaccine field.
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