Vaccines for Mycoplasma Diseases of Small Ruminants: A Neglected Area of Research

Mycoplasmas cause some of the most economically important diseases of sheep and goats, including diseases listed by the World Organisation for Animal Health (OIE) such as contagious caprine pleuropneumonia (CCPP) and contagious agalactia (CA). Other important mycoplasma diseases include chronic respiratory and arthritic syndrome (CRAS) and atypical pneumonia, both present on all continents where small ruminants are farmed. Unfortunately, owing to a lack of investment, most commercial vaccines for these diseases are of poor quality, being mostly composed of killed bacteriocins of dubious or unknown efficacy. Several Mediterranean laboratories produce autogenous vaccines, but these can only be used on farms where outbreaks have been officially declared, and consequently have limited impact on disease nationally. Effective live vaccines are available, but their use is often restricted because of safety concerns. With the necessary safeguards in place, we argue for their greater use. This review examines reported vaccines for mycoplasma diseases of small ruminants and attempts to identify new candidate antigens that may enable the development of improved products. Vaccines for CCPP are covered elsewhere.

Next-Generation Vaccines Based on Self-Amplifying RNA

Recently, nucleic acid-based RNA and DNA vaccines have represented a better solution to avoid infectious diseases than “traditional” live and non-live vaccines. Synthetic RNA and DNA molecules allow scalable, rapid, and cell-free production of vaccines in response to an emerging disease such as the current COVID-19 pandemic. The development process begins with laboratory transcription of sequences encoding antigens, which are then formulated for delivery. The various potent of RNA over live and inactivated viruses are proven by advances in delivery approaches. These vaccines contain no infectious elements nor the risk of stable integration with the host cell genome compared to conventional vaccines. Conventional mRNA-based vaccines transfer genes of interest (GOI) of attenuated mRNA viruses to individual host cells. Synthetic mRNA in liposomes forms a modern, refined sample, resulting in a safer version of live attenuated RNA viruses. Self-amplifying RNA (saRNA) is a replicating version of mRNA-based vaccines that encode both (GOI) and viral replication machinery. saRNA is required at lower doses than conventional mRNA, which may improve immunization. Here we provide an overview of current mRNA vaccine approaches, summarize highlight challenges and recent successes, and offer perspectives on the future of mRNA vaccines.

Does Influenza Vaccination during Pregnancy Have Effects on Non-Influenza Infectious Morbidity? A Systematic Review and Meta-Analysis of Randomised Controlled Trials

The recommendation to provide inactivated influenza vaccine (IIV) to pregnant women is based on observed protection against influenza-related morbidity in mother and infant. Non-live vaccines may have non-specific effects (NSEs), increasing the risk of non-targeted infections in females. We reviewed the evidence from available randomised controlled trials (RCTs) of IIV to pregnant women, to assess whether IIV may have NSEs. Four RCTs, all conducted in low- and middle-income settings, were identified. We extracted information on all-cause and infectious mortality and adverse events in women and their infants. We conducted meta-analyses providing risk ratios (RR). The meta-analysis for maternal all-cause mortality provided a RR of 1.48 (95% CI = 0.52–4.16). The estimates for miscarriage/stillbirth and infant all-cause mortality up to 6 months of age were 1.06 (0.78–1.44) and 1.11 (0.87–1.41), respectively. IIV was associated with a higher risk of non-influenza infectious adverse events, with meta-estimates of 2.01 (1.15–3.50) in women and 1.36 (1.12–1.67) in infants up to 6 months of age. Thus, following a pattern seen for other non-live vaccines, IIV was associated with a higher risk of non-influenza infectious adverse events. To ensure that scarce resources are used well, and no harm is inflicted, further RCTs are warranted.

Delay in assessing vitamin D supplements and live vaccines for tuberculosis, polio, and measles to protect people from Covid-19

Introduction: In March 2020, less than three months after China reported a cluster of pneumonia cases in Wuhan, the United States (US) government budgeted money to support development of Covid-19 vaccines. By mid-December 2020, two had been developed, tested, and received the US government’s experimental use authorization. Given evidence that vitamin D supplements and live vaccines for tuberculosis, polio, and measles reduce risks for acute respiratory infection, many experts hypothesized they might reduce risks for Covid-19 infection. Expedited randomized controlled trials, as done for Covid-19 vaccines, could have assessed their protection against C19 no later than end-July 2020. Methods: On 21 April 2021, I searched trial registries maintained by the US National Institutes of Medicine and the World Health Organization for trials with ≥400 participants to assess vitamin D or live vaccines to prevent Covid-19 infections (all or symptomatic). On 10-13 November 2021, I searched PubMed and medRxiv for results reported from these trials.Results: In April 2021, I found 32 trials (9 for vitamin D and 23 for live vaccines) proposing to assess the impact of these interventions on rates of new Covid-19 infections (all or symptomatic). Only 10 trials proposed to begin by June 2020, and only one to end in 2020. My search on 10-13 November 2021, almost 11 months after the US approved the first two Covid-19 vaccines, found results reported from only one of the 32 trials (live measles vaccine significantly reduced new symptomatic infections). Conclusions: If health experts had demonstrated similar urgency in assessing vitamin D supplements and live vaccines for tuberculosis, polio, and measles as in developing Covid-19 vaccines, trials could have reported by end-July 2020. Depending on what trials reported, these interventions could have prevented a large percentage of more than 600,000 Covid-19 deaths reported in the US from August 2020 through November 2021. Delay in assessing vitamin D has racial implications as well, since vitamin D deficiency and Covid-19 deaths in the US have been far more common among Blacks and Hispanics compared to Whites. Going forward, depending on what trials report, these interventions could help people live with Covid-19 as an endemic virus.

Effect of Antibiotics on the Colonization of Live Attenuated Salmonella Enteritidis Vaccine in Chickens

Salmonellosis, caused by Salmonella Enteritidis, is a prevalent zoonosis that has serious consequences for human health and the development of the poultry sector. The Salmonella Enteritis live vaccine (Sm24/Rif12/Ssq strain) is used to prevent Salmonella Enteritidis around the world. However, in some parts of the world, poultry flocks are frequently raised under intensive conditions, with significant amounts of antimicrobials to prevent and treat disease and to promote growth. To investigate whether antibiotic use influences the colonization of orally administered Salmonella live vaccines, 240 1-day-old specific pathogen-free chicks were randomly divided into 24 groups of 10 animals for this study. The different groups were treated with different antibiotics, which included ceftiofur, amoxicillin, enrofloxacin, and lincomycin–spectinomycin. Each group was immunized 2, 3, 4, and 5 days after withdrawal, respectively. At 5 days after immunization, the blood, liver, and ceca with contents were collected for the isolation of the Salmonella live vaccine strain. The result showed that no Salmonella vaccine strain was isolated in the blood and liver of the chicks in those groups. The highest number of Salmonella vaccine strains was isolated in the cecum from chicks vaccinated 2 days after ceftiofur withdrawal, and no Salmonella vaccine strain was isolated from the cecum in chicks immunized 3 days after ceftiofur withdrawal. Among the chickens immunized 4 days after the withdrawal of amoxicillin, enrofloxacin, and lincomycin–spectinomycin, the number of Salmonella vaccine colonization in the cecum was the highest, which was higher than that of the chickens immunized at other withdrawal interval (2, 3, and 5 days) groups and was higher than that of the chickens without treatment (P < 0.05). This study provides a reference for the effective use of the Salmonella Enteritidis live vaccine and key antibiotics commonly utilized in the poultry industry.

Effectiveness and Safety of Vaccination in Patients with Juvenile Idiopathic Arthritis

Background. Vaccination is the most effective method for reducing morbidity, disability, mortality from of various infections. However, there was a view for a long time that vaccines are ineffective and unsafe to use in people with rheumatological diseases, including juvenile idiopathic arthritis (JIA). Objective.The aim of the study is to analyze literature data on safety and efficacy of vaccination for JIA patients with live and non-live vaccines.Methods: literature analysis was based on data from medical databases PubMed and Google Scholar.Results. Both live and non-live vaccines are safe and immunogenic enough for children with JIA. Most studies confirm vaccination efficacy in patients with JIA when using glucocorticosteroids (GCS) and methotrexate, while therapy with disease-modifying antirheumatic drugs (DMARD) can reduce antibody titers over time. In general, antibodies levels preservation in previously vaccinated children with JIA is less than in global population. This indicates the need to administer booster doses for such patients. No adverse effects on the course of primary disease after vaccination and no post-vaccine complications were revealed.Conclusion. Vaccination of patients with JIA should be performed with reference to the therapy that the patient already receives, under the control of antibodies level. Booster doses should be implemented in case of titers decrease below the protective levels.

Vaccine Types

Vaccines are biological preparations, often made from attenuated or killed forms of microorganisms or fractions thereof. They work by stimulating the immune system to produce antibodies and cells directed against a particular organism, mimicking "natural infection". Based on their biological and chemical characteristics, vaccines can be categorized into two basic types, "Live-attenuated" (bacterial or viral) vaccines and "inactivated" or "non-live" vaccines. Examples of live-attenuated vaccines include: measles-, mumps-, and rubella-, varicella-, yellow fever-, oral polio- (OPV), rotavirus-, ("nasal-spray") live-attenuated influenza- (LAIV), and BCG-vaccine. Attenuation results in micro-organisms that may still infect and multiply in humans, but they do not cause disease. Some of these vaccines are associated with life-long immunity. Inactivated or non-live vaccines include those against hepatitis A, influenza, pertussis, rabies or the polysaccharide vaccines directed against encapsulated bacteria (Haemophilus influenzae type b, Streptococcus pneumoniae, Neisseria meningitidis). Most non-live vaccines generally require additional doses ("boosters") to maintain long-term protective immunity. There are many other subcategories of these basic groups, like subunit vaccines, whole cell vaccines, toxoid vaccines, polysaccharide vaccines, recombinant protein vaccines, mucosal vaccines, or DNA-, mRNA- and vector-vaccines.

Vaccination Schedules

First vaccines and vaccination schedules were based on “trial and error” and on immunogenicity data (serology). Latest since the 1990s, vaccination schedules are based on well-defined phase 1–3 development programs as basis for licensure of any new product. Vaccination schedules must bear in mind the epidemiology of the targeted disease; the biology of available vaccine product(s); local opportunities to vaccinate; monitoring for the desired outcome. There are 4 basic primary vaccination schedules for children, based on historical development and local needs. Birth doses are recommended with BCG and hepatitis B vaccine. Dosing in the 2nd year of life is usually needed for long term-protection induced by polysaccharide-conjugate vaccines. Live vaccines (MMR, VZV) are usually given as of 9 months of age – later dosing may induce improved immune responses; a second dose is needed before school entry for optimal protection. In addition to “general regular schedules” vaccines and schedules emerge for pregnant women, international travelers, persons above 60 or 65 years, immunocompromised hosts.

Evaluation of the Cross-Protective Efficacy of a Chimeric PRRSV Vaccine against Two Genetically Diverse PRRSV2 Field Strains in a Reproductive Model

Despite the routine use of porcine reproductive and respiratory syndrome (PRRS)-modified live vaccines, serious concerns are currently being raised due to their quick reversion to virulence and limited cross-protection against divergent PRRS virus (PRRSV) strains circulating in the field. Therefore, a PRRS chimeric vaccine (JB1) was produced using a DNA-launched infectious clone by replacing open reading frames (ORFs) 3–6 with those from a mixture of two genetically different PRRSV2 strains (K07–2273 and K08–1054) and ORF1a with that from a mutation-resistant PRRSV strain (RVRp22) exhibiting an attenuated phenotype. To evaluate the safety and cross-protective efficacy of JB1 in a reproductive model, eight PRRS-negative pregnant sows were purchased and divided into four groups. Four sows in two of the groups were vaccinated with JB1, and the other 4 sows were untreated at gestational day 60. At gestational day 93, one vaccinated group and one nonvaccinated group each were challenged with either K07–2273 or K08–1054. All of the sows aborted or delivered until gestation day 115 (24 days post challenge), and the newborn piglets were observed up to the 28th day after birth, which was the end of the experiment. Overall, pregnant sows of the JB1-vaccinated groups showed no meaningful viremia after vaccination and significant reductions in viremia with K07–2273 and K08–1054, exhibiting significantly higher levels of serum virus-neutralizing antibodies than non-vaccinated sows. Moreover, the JB1-vaccinated groups did not exhibit any abortion due to vaccination and showed improved piglet viability and birth weight. The piglets from JB1-vaccinated sows displayed lower viral concentrations in serum and fewer lung lesions compared with those of the piglets from the nonvaccinated sows. Therefore, JB1 is a safe and effective vaccine candidate that confers simultaneous protection against two genetically different PRRSV strains.