Novel approaches for vaccine development.

Vaccines are critical tools for maintaining global health. Traditional vaccine technologies have been used across a wide range of bacterial and viral pathogens, yet there are a number of examples where they have not been successful, such as for persistent infections, rapidly evolving pathogens with high sequence variability, complex viral antigens, and emerging pathogens. Novel technologies such as nucleic acid and viral vector vaccines offer the potential to revolutionize vaccine development as they are well-suited to address existing technology limitations. In this review, we discuss the current state of RNA vaccines, recombinant adenovirus vector-based vaccines, and advances from biomaterials and engineering that address these important public health challenges.

Messenger RNA vaccines against SARS-CoV-2.

The first two vaccines proven to be effective for inhibiting COVID-19 illness were both mRNA, achieving 95% efficacy (and safety) among 74,000 participants (half receiving placebo) after intramuscular delivery of two shots, 3-4 weeks apart. To view this Bench to Bedside, open or download the PDF.

Recombinant or Standard-Dose Influenza Vaccine in Adults under 65 Years of Age.

BACKGROUND: Quadrivalent recombinant influenza vaccines contain three times the amount of hemagglutinin protein as standard-dose egg-based vaccines, and the recombinant formulation is not susceptible to antigenic drift during manufacturing. Data are needed on the relative effectiveness of recombinant vaccines as compared with standard-dose vaccines against influenza-related outcomes in adults under the age of 65 years. METHODS: In this cluster-randomized observational study, Kaiser Permanente Northern California facilities routinely administered either a high-dose recombinant influenza vaccine (Flublok Quadrivalent) or one of two standard-dose influenza vaccines during the 2018-2019 and 2019-2020 influenza seasons to adults 50 to 64 years of age (primary age group) and 18 to 49 years of age. Each facility alternated weekly between the two vaccine formulations. The primary outcome was influenza (A or B) confirmed by polymerase-chain-reaction (PCR) testing. Secondary outcomes included influenza A, influenza B, and influenza-related hospitalization outcomes. We used Cox regression analysis to estimate the hazard ratio of the recombinant vaccine as compared with the standard-dose vaccines against each outcome. We calculated the relative vaccine effectiveness as 1 minus the hazard ratio. RESULTS: The study population included 1,630,328 vaccinees between the ages of 18 and 64 years (632,962 in the recombinant-vaccine group and 997,366 in the standard-dose group). During this study period, 1386 cases of PCR-confirmed influenza were diagnosed in the recombinant-vaccine group and 2435 cases in the standard-dose group. Among the participants who were 50 to 64 years of age, 559 participants (2.00 cases per 1000) tested positive for influenza in the recombinant-vaccine group as compared with 925 participants (2.34 cases per 1000) in the standard-dose group (relative vaccine effectiveness, 15.3%; 95% confidence interval [CI], 5.9 to 23.8; P = 0.002). In the same age group, the relative vaccine effectiveness against influenza A was 15.7% (95% CI, 6.0 to 24.5; P = 0.002). The recombinant vaccine was not significantly more protective against influenza-related hospitalization than were the standard-dose vaccines. CONCLUSIONS: The high-dose recombinant vaccine conferred more protection against PCR-confirmed influenza than an egg-based standard-dose vaccine among adults between the ages of 50 and 64 years. (Funded by Sanofi; ClinicalTrials.gov number, NCT03694392.).

BNT162b2 Protection against the Omicron Variant in Children and Adolescents.

BACKGROUND: Spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.529 (omicron) variant, which led to increased U.S. hospitalizations for coronavirus disease 2019 (Covid-19), generated concern about immune evasion and the duration of protection from vaccines in children and adolescents. METHODS: Using a case-control, test-negative design, we assessed vaccine effectiveness against laboratory-confirmed Covid-19 leading to hospitalization and against critical Covid-19 (i.e., leading to receipt of life support or to death). From July 1, 2021, to February 17, 2022, we enrolled case patients with Covid-19 and controls without Covid-19 at 31 hospitals in 23 states. We estimated vaccine effectiveness by comparing the odds of antecedent full vaccination (two doses of BNT162b2 messenger RNA vaccine) at least 14 days before illness among case patients and controls, according to time since vaccination for patients 12 to 18 years of age and in periods coinciding with circulation of B.1.617.2 (delta) (July 1, 2021, to December 18, 2021) and omicron (December 19, 2021, to February 17, 2022) among patients 5 to 11 and 12 to 18 years of age. RESULTS: We enrolled 1185 case patients (1043 [88%] of whom were unvaccinated, 291 [25%] of whom received life support, and 14 of whom died) and 1627 controls. During the delta-predominant period, vaccine effectiveness against hospitalization for Covid-19 among adolescents 12 to 18 years of age was 93% (95% confidence interval [CI], 89 to 95) 2 to 22 weeks after vaccination and was 92% (95% CI, 80 to 97) at 23 to 44 weeks. Among adolescents 12 to 18 years of age (median interval since vaccination, 162 days) during the omicron-predominant period, vaccine effectiveness was 40% (95% CI, 9 to 60) against hospitalization for Covid-19, 79% (95% CI, 51 to 91) against critical Covid-19, and 20% (95% CI, -25 to 49) against noncritical Covid-19. During the omicron period, vaccine effectiveness against hospitalization among children 5 to 11 years of age was 68% (95% CI, 42 to 82; median interval since vaccination, 34 days). CONCLUSIONS: BNT162b2 vaccination reduced the risk of omicron-associated hospitalization by two thirds among children 5 to 11 years of age. Although two doses provided lower protection against omicron-associated hospitalization than against delta-associated hospitalization among adolescents 12 to 18 years of age, vaccination prevented critical illness caused by either variant. (Funded by the Centers for Disease Control and Prevention.).

BNT162b2 Vaccine Effectiveness against Omicron in Children 5 to 11 Years of Age.

BACKGROUND: Limited evidence is available on the real-world effectiveness of the BNT162b2 vaccine against coronavirus disease 2019 (Covid-19) and specifically against infection with the omicron variant among children 5 to 11 years of age. METHODS: Using data from the largest health care organization in Israel, we identified a cohort of children 5 to 11 years of age who were vaccinated on or after November 23, 2021, and matched them with unvaccinated controls to estimate the vaccine effectiveness of BNT162b2 among newly vaccinated children during the omicron wave. Vaccine effectiveness against documented severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and symptomatic Covid-19 was estimated after the first and second vaccine doses. The cumulative incidence of each outcome in the two study groups through January 7, 2022, was estimated with the use of the Kaplan-Meier estimator, and vaccine effectiveness was calculated as 1 minus the risk ratio. Vaccine effectiveness was also estimated in age subgroups. RESULTS: Among 136,127 eligible children who had been vaccinated during the study period, 94,728 were matched with unvaccinated controls. The estimated vaccine effectiveness against documented infection was 17% (95% confidence interval [CI], 7 to 25) at 14 to 27 days after the first dose and 51% (95% CI, 39 to 61) at 7 to 21 days after the second dose. The absolute risk difference between the study groups at days 7 to 21 after the second dose was 1905 events per 100,000 persons (95% CI, 1294 to 2440) for documented infection and 599 events per 100,000 persons (95% CI, 296 to 897) for symptomatic Covid-19. The estimated vaccine effectiveness against symptomatic Covid-19 was 18% (95% CI, -2 to 34) at 14 to 27 days after the first dose and 48% (95% CI, 29 to 63) at 7 to 21 days after the second dose. We observed a trend toward higher vaccine effectiveness in the youngest age group (5 or 6 years of age) than in the oldest age group (10 or 11 years of age). CONCLUSIONS: Our findings suggest that as omicron was becoming the dominant variant, two doses of the BNT162b2 messenger RNA vaccine provided moderate protection against documented SARS-CoV-2 infection and symptomatic Covid-19 in children 5 to 11 years of age. (Funded by the European Union through the VERDI project and others.).

Post-mRNA vaccine flares in autoimmune inflammatory rheumatic diseases: Results from the COronavirus National Vaccine registry for ImmuNe diseases SINGapore (CONVIN-SING).

BACKGROUND: Studies of flares of autoimmune inflammatory rheumatic diseases (AIIRD) after COVID-19 mRNA vaccination are limited by small sample size, short follow up or at risk of selection bias. METHODS: A national retrospective cohort study of consecutive AIIRD patients ≥12 years old, across 8 hospitals who received at least one dose of a COVID-19 mRNA vaccine. Patients were included from the date of 1st vaccine dose and censored at the time of flare or on the date of the clinic visit at least 3 months from cohort entry, whichever came first. Predictors of flare were determined by Cox proportional hazards analysis. FINDINGS: 4627 patients (73% Chinese, 71% female) of median (IQR) age 61 (48, 70) years were included; 42% Rheumatoid arthritis, 14% Systemic lupus erythematosus and 11% Psoriatic arthritis. 47% were in remission, 41% low disease activity, 10% moderate disease activity and 1% in high disease activity. 18% patients flared, of which 11.7% were within the 3-month period of interest. 11.8% patients improved. Median (IQR) time-to-flare was 60 (30, 114) days. 25% flares were self-limiting, 61% mild-moderate and 14% severe. Older patients (53-65 years and >66 years) had a lower risk of flare [HR 0.6 (95% CI 0.5-0.8) and 0.7 (0.6-0.8) respectively]. Patients with inflammatory arthritis and with active disease had a higher risk of flare [HR 1.5 (1.2-2.0) and 1.4 (1.2-1.6), respectively]. Treatment with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), immunosuppression and prednisolone was also associated with an increased risk of flare [HR 1.5 (1.1-2), 1.2 (1.1-1.4) and 1.5 (1.2-1.8) for prednisolone ≤7.5 mg respectively]. INTERPRETATION: There was a moderately high rate of AIIRD flares after mRNA vaccination but also improvement in several patients. Severe flares and hospitalisation were rare. Thus, vaccination remains safe and highly recommended.

Use of Recombinant Zoster Vaccine in Immunocompromised Adults Aged ≥19 Years: Recommendations of the Advisory Committee on Immunization Practices - United States, 2022.

Zoster Vaccine Recombinant, Adjuvanted (Shingrix, GlaxoSmithKline [GSK]) is a 2-dose (0.5 mL each) subunit vaccine containing recombinant glycoprotein E in combination with adjuvant (AS01B) that was licensed in the United States for prevention of herpes zoster for adults aged ≥50 years by the Food and Drug Administration (FDA) and recommended for immunocompetent adults aged ≥50 years by the Advisory Committee on Immunization Practices (ACIP) in 2017* (1). On July 23, 2021, the FDA expanded the indication for recombinant zoster vaccine (RZV) to include adults aged ≥18 years who are or will be at increased risk for herpes zoster because of immunodeficiency or immunosuppression caused by known disease or therapy (2). On October 20, 2021, ACIP recommended 2 doses of RZV for the prevention of herpes zoster and related complications in adults aged ≥19 years† who are or will be immunodeficient or immunosuppressed because of disease or therapy. RZV is the first herpes zoster vaccine approved for use in immunocompromised persons. With moderate to high vaccine efficacy and an acceptable safety profile, RZV has the potential to prevent considerable herpes zoster incidence and related complications. This report updates previous ACIP recommendations for the prevention of herpes zoster (1,3).

Adverse effects following COVID-19 vaccination in Iran.

BACKGROUND: Vaccination is a key intervention to prevent COVID-19. Many vaccines are administered globally, yet there is not much evidence regarding their safety and adverse effects. Iran also faces this challenge, especially as data regarding the Sputnik V vaccine is sparse. Therefore, the aim of this study is to determine the adverse effects of the most commonly used vaccines in Iran. METHODS: Using a retrospective cohort study design, 6600 subjects aged 18 years or older who had received two doses of any of the three COVID-19 vaccines (Sinopharm, AstraZeneca, and Sputnik V) were selected using a random sampling method between March and August 2021. Subjects were asked about any adverse effects of the vaccines by trained interviewers via telephone interview. Vaccine-related adverse effects in individuals during the first 72 h and subsequently following both doses of the vaccines were determined. The demographic variables, type of administered vaccine, adverse effects, and history of the previous infection with COVID-19 were collected. Descriptive statistics (mean, standard deviation) and analytical statistics (Chi-squared and Wilcoxon tests) were performed at a 95% significance level using STATA software version 15 (STATA Corp, College Station, TX, USA). RESULTS: From 6600 participants, 4775 responded (response rate = 72.3%). Of the participants, 1460 (30.6%) received the AstraZeneca vaccine, 1564 (32.8%) received the Sinopharm vaccine and 1751 (36.7%) received the Sputnik V vaccine. 2653 participants (55.56%) reported adverse effects after the first dose and 1704 (35.7%) after the second dose. Sputnik V caused the most adverse effects with 1449 (82.7%) vaccine recipients reporting symptoms after the first or second dose, compared with 1030 (70.5%) for AstraZeneca and only 585 (37.4%) for the Sinopharm vaccine. The most common adverse effects after the first dose were fatigue (28.37%), chill/fever (26.86%), and skeletal pain (22.38%). These three adverse effects were the same for the second dose, although their prevalence was lower. CONCLUSIONS: In this study, we demonstrate that the Sputnik V vaccine has the highest rate of adverse effects, followed by the AstraZeneca and Sinopharm vaccines. COVID-19 vaccines used in Iran are safe and there were no reports of serious adverse effects.

Safety of Recombinant Zoster Vaccine in Rheumatology Patients.

OBJECTIVES: Recombinant zoster vaccine (RZV) is Food and Drug Administration approved for the prevention of herpes zoster (shingles) in adults 50 years old and older. Immunocompromised subjects were excluded from the pivotal vaccine trials. We studied the safety of this vaccine in our university-affiliated rheumatology practice. METHODS: This was a single-center, retrospective study focusing on subjects who received RZV during 2018. We collected the demographic data, any self-reported adverse events after vaccination, C-reactive protein, Routine Assessment of Patient Index Data 3 (RAPID3) scores for subjects with rheumatoid arthritis, and available RAPID3 scores for all study subjects before and after the vaccination. RESULTS: Comparision of C-reactive protein (n = 40), RAPID3 scores for subjects with rheumatoid arthritis (n = 16), and available RAPID3 scores for all subjects (n = 21) using the paired t test, did not show significant differences before and after the administration of RZV. A total of 6.4% of patients reported adverse events after vaccination. The adverse events were mild and did not lead to hospitalization, end organ damage, or change in treatment plan. CONCLUSIONS: The RZV was safe and well tolerated among our study population.

[Varicella-zoster virus (VZV) acute retinal necrosis and recombinant zoster vaccine]. / Nécrose rétinienne aiguë due au virus de la varicelle et du zona et vaccin recombinant contre le zona.

Varicella zoster virus (VZV) is responsible for chickenpox. Like all herpes viruses, after primary infection it enters into latency and can be reactivated afterwards. Many forms of symptomatic reactivation of VZV exist including acute retinal necrosis (ARN), an ophthalmic emergency which can lead to blindness. ARN is treated starting with high-dose intravenous acyclovir then with oral valaciclovir for a total duration of up to 3 months. Symptomatic reactivations of VZV are public health issues. The new Swiss 2022 vaccination plan includes the recombinant vaccine Shingrix. It effectively prevents VZV symptomatic reactivations even in elderly and immuno suppressed patients.

Le virus de la varicelle et du zona (VZV) est responsable de la varicelle. Comme tous les virus herpétiques, après la primo-infection, il entre en latence et peut se réactiver plus tard. Il existe de nombreuses formes de réactivations symptomatiques du VZV, dont la nécrose rétinienne aiguë (NRA), qui est une urgence ophtalmique pouvant aboutir à la cécité. La NRA est traitée par aciclovir intraveineux à haute dose dans sa prise en charge initiale puis par valaciclovir per os pour une durée totale pouvant aller jusqu'à 3 mois. Les réactivations symptomatiques de VZV sont un enjeu de santé publique. Le nouveau plan de vaccination suisse 2022 intègre le vaccin recombinant Shingrix, qui permet de prévenir efficacement les réactivations symptomatiques de VZV chez les patients même âgés et immunosupprimés.

mRNA vaccine: a potential therapeutic strategy.

mRNA vaccines have tremendous potential to fight against cancer and viral diseases due to superiorities in safety, efficacy and industrial production. In recent decades, we have witnessed the development of different kinds of mRNAs by sequence optimization to overcome the disadvantage of excessive mRNA immunogenicity, instability and inefficiency. Based on the immunological study, mRNA vaccines are coupled with immunologic adjuvant and various delivery strategies. Except for sequence optimization, the assistance of mRNA-delivering strategies is another method to stabilize mRNAs and improve their efficacy. The understanding of increasing the antigen reactiveness gains insight into mRNA-induced innate immunity and adaptive immunity without antibody-dependent enhancement activity. Therefore, to address the problem, scientists further exploited carrier-based mRNA vaccines (lipid-based delivery, polymer-based delivery, peptide-based delivery, virus-like replicon particle and cationic nanoemulsion), naked mRNA vaccines and dendritic cells-based mRNA vaccines. The article will discuss the molecular biology of mRNA vaccines and underlying anti-virus and anti-tumor mechanisms, with an introduction of their immunological phenomena, delivery strategies, their importance on Corona Virus Disease 2019 (COVID-19) and related clinical trials against cancer and viral diseases. Finally, we will discuss the challenge of mRNA vaccines against bacterial and parasitic diseases.

Tumor-antigens and immune landscapes identification for prostate adenocarcinoma mRNA vaccine.

Prostate adenocarcinoma (PRAD) is a leading cause of death among men. Messenger ribonucleic acid (mRNA) vaccine presents an attractive approach to achieve satisfactory outcomes; however, tumor antigen screening and vaccination candidates show a bottleneck in this field. We aimed to investigate the tumor antigens for mRNA vaccine development and immune subtypes for choosing appropriate patients for vaccination. We identified eight overexpressed and mutated tumor antigens with poor prognostic value of PRAD, including KLHL17, CPT1B, IQGAP3, LIME1, YJEFN3, KIAA1529, MSH5 and CELSR3. The correlation of those genes with antigen-presenting immune cells were assessed. We further identified three immune subtypes of PRAD (PRAD immune subtype [PIS] 1-3) with distinct clinical, molecular, and cellular characteristics. PIS1 showed better survival and immune cell infiltration, nevertheless, PIS2 and PIS3 showed cold tumor features with poorer prognosis and higher tumor genomic instability. Moreover, these immune subtypes presented distinguished association with immune checkpoints, immunogenic cell death modulators, and prognostic factors of PRAD. Furthermore, immune landscape characterization unraveled the immune heterogeneity among patients with PRAD. To summarize, our study suggests KLHL17, CPT1B, IQGAP3, LIME1, YJEFN3, KIAA1529, MSH5 and CELSR3 are potential antigens for PRAD mRNA vaccine development, and patients in the PIS2 and PIS3 groups are more suitable for vaccination.

Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomised, first-in-human trial.

BACKGROUND: A vaccine to protect against COVID-19 is urgently needed. We aimed to assess the safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 (Ad5) vectored COVID-19 vaccine expressing the spike glycoprotein of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain. METHODS: We did a dose-escalation, single-centre, open-label, non-randomised, phase 1 trial of an Ad5 vectored COVID-19 vaccine in Wuhan, China. Healthy adults aged between 18 and 60 years were sequentially enrolled and allocated to one of three dose groups (5 × 1010, 1 × 1011, and 1·5 × 1011 viral particles) to receive an intramuscular injection of vaccine. The primary outcome was adverse events in the 7 days post-vaccination. Safety was assessed over 28 days post-vaccination. Specific antibodies were measured with ELISA, and the neutralising antibody responses induced by vaccination were detected with SARS-CoV-2 virus neutralisation and pseudovirus neutralisation tests. T-cell responses were assessed by enzyme-linked immunospot and flow-cytometry assays. This study is registered with ClinicalTrials.gov, NCT04313127. FINDINGS: Between March 16 and March 27, 2020, we screened 195 individuals for eligibility. Of them, 108 participants (51% male, 49% female; mean age 36·3 years) were recruited and received the low dose (n=36), middle dose (n=36), or high dose (n=36) of the vaccine. All enrolled participants were included in the analysis. At least one adverse reaction within the first 7 days after the vaccination was reported in 30 (83%) participants in the low dose group, 30 (83%) participants in the middle dose group, and 27 (75%) participants in the high dose group. The most common injection site adverse reaction was pain, which was reported in 58 (54%) vaccine recipients, and the most commonly reported systematic adverse reactions were fever (50 [46%]), fatigue (47 [44%]), headache (42 [39%]), and muscle pain (18 [17%]. Most adverse reactions that were reported in all dose groups were mild or moderate in severity. No serious adverse event was noted within 28 days post-vaccination. ELISA antibodies and neutralising antibodies increased significantly at day 14, and peaked 28 days post-vaccination. Specific T-cell response peaked at day 14 post-vaccination. INTERPRETATION: The Ad5 vectored COVID-19 vaccine is tolerable and immunogenic at 28 days post-vaccination. Humoral responses against SARS-CoV-2 peaked at day 28 post-vaccination in healthy adults, and rapid specific T-cell responses were noted from day 14 post-vaccination. Our findings suggest that the Ad5 vectored COVID-19 vaccine warrants further investigation. FUNDING: National Key R&D Program of China, National Science and Technology Major Project, and CanSino Biologics.

Semi- and fully synthetic carbohydrate vaccines against pathogenic bacteria: recent developments.

The importance of vaccine-induced protection was repeatedly demonstrated over the last three decades and emphasized during the recent COVID-19 pandemic as the safest and most effective way of preventing infectious diseases. Vaccines have controlled, and in some cases, eradicated global viral and bacterial infections with high efficiency and at a relatively low cost. Carbohydrates form the capsular sugar coat that surrounds the outer surface of human pathogenic bacteria. Specific surface-exposed bacterial carbohydrates serve as potent vaccine targets that broadened our toolbox against bacterial infections. Since first approved for commercial use, antibacterial carbohydrate-based vaccines mostly rely on inherently complex and heterogenous naturally derived polysaccharides, challenging to obtain in a pure, safe, and cost-effective manner. The introduction of synthetic fragments identical with bacterial capsular polysaccharides provided well-defined and homogenous structures that resolved many challenges of purified polysaccharides. The success of semisynthetic glycoconjugate vaccines against bacterial infections, now in different phases of clinical trials, opened up new possibilities and encouraged further development towards fully synthetic antibacterial vaccine solutions. In this mini-review, we describe the recent achievements in semi- and fully synthetic carbohydrate vaccines against a range of human pathogenic bacteria, focusing on preclinical and clinical studies.

Site-Specific and Stable Conjugation of the SARS-CoV-2 Receptor-Binding Domain to Liposomes in the Absence of Any Other Adjuvants Elicits Potent Neutralizing Antibodies in BALB/c Mice.

Understanding immune responses toward viral infection will be useful for potential therapeutic intervention and offer insights into the design of prophylactic vaccines. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the COVID-19 pandemic. To understand the complex immune responses toward SARS-CoV-2 infection, here we developed a method to express and purify the recombinant and engineered viral receptor-binding domain (RBD) to more than 95% purity. We could encapsulate RNA molecules into the interior of a virion-sized liposome. We conjugated the purified RBD proteins onto the surface of the liposome in an orientation-specific manner with defined spatial densities. Both the encapsulation of RNAs and the chemical conjugation of the RBD protein on liposome surfaces were stable under physiologically relevant conditions. In contrast to soluble RBD proteins, a single injection of RBD-conjugated liposomes alone, in the absence of any other adjuvants, elicited RBD-specific B cell responses in BALB/c mice, and the resulting animal sera could potently neutralize HIV-1 pseudovirions that displayed the SARS-CoV-2 spike proteins. These results validate these supramolecular structures as a novel and effective tool to mimic the structure of enveloped viruses, the use of which will allow systematic dissection of the complex B cell responses to SARS-CoV-2 infection.

Safety of mRNA-Based Vaccines for SARS CoV-2.

SARS-CoV-2 has infected more than 100 million people, causing 2 million deaths globally. Studies on the development of a vaccine ended up with different formulations. We herein discuss the safety record of the two approved vaccines.

Is there a role for childhood vaccination against COVID-19?

Tremendous efforts are undertaken to quickly develop COVID-19 vaccines that protect vulnerable individuals from severe disease and thereby limit the health and socioeconomic impacts of the pandemic. Potential candidates are tested in adult populations, and questions arise of whether COVID-19 vaccination should be implemented in children. Compared to adults, the incidence and disease severity of COVID-19 are low in children, and despite their infectiveness, their role in disease propagation is limited. Therefore, COVID-19 vaccines will need to have fully demonstrated safety and efficacy in preventing not only complications but transmission to justify childhood vaccination. This work summarizes currently tested vaccine platforms and debates practical and ethical considerations for their potential use in children. It also discusses the already deleterious effect of the pandemic on routine childhood vaccine coverage, calling for action to limit the risks for a rise in vaccine-preventable diseases.

Protection studies of an excretory-secretory protein HcABHD against Haemonchus contortus infection.

Unlike the successful immunization of native H. contortus antigens that contributed to the realization of the first commercial vaccine Barbervax, not many studies revealed the encouraging protective efficacies of recombinant H. contortus antigens in laboratory trials or under field conditions. In our preliminary study, H. contortus α/ß-hydrolase domain protein (HcABHD) was demonstrated to be an immunomodulatory excretory-secretory (ES) protein that interacts with goat T cells. We herein evaluated the protective capacities of two HcABHD preparations, recombinant HcABHD (rHcABHD) antigen and anti-rHcABHD IgG, against H. contortus challenge via active and passive immunization trials, respectively. Parasitological parameter, antibody responses, hematological pathology and cytokine profiling in unchallenged and challenged goats were monitored and determined throughout both trials. Subcutaneous administration of rHcABHD with Freund adjuvants elicited protective immune responses in challenged goats, diminishing cumulative fecal egg counts (FEC) and total worm burden by 54.0% and 74.2%, respectively, whereas passive immunization with anti-rHcABHD IgG conferred substantial protection to challenged goats by generating a 51.5% reduction of cumulative FEC and a 73.8% reduction of total worm burden. Additionally, comparable changes of mucosal IgA levels, circulating IgG levels, hemoglobin levels, and serum interleukin (IL)-4 and IL-17A levels were observed in rHcABHD protein/anti-rHcABHD IgG immunized goats in both trials. Taken together, the recombinant version of HcABHD might have further application under field conditions in protecting goats against H. contortus infection, and the integrated immunological pipeline of ES antigen identification, screening and characterization may provide new clues for further development of recombinant subunit vaccines to control H. contortus.