Design and computational evaluation of a novel multi-epitope hybrid vaccine against monkeypox virus: Potential targets and immunogenicity assessment for pandemic preparedness.

Monkeypox is a type of DNA-enveloped virus that belongs to the orthopoxvirus family, closely related to the smallpox virus. It can cause an infectious disease in humans known as monkeypox disease. Although there are multiple drugs and vaccines designed to combat orthopoxvirus infections, with a primary focus on smallpox, the recent spread of the monkeypox virus to over 50 countries have ignited a mounting global concern. This unchecked viral proliferation has raised apprehensions about the potential for a pandemic corresponding to the catastrophic impact of COVID-19. This investigation explored the structural proteins of monkeypox virus as potential candidates for designing a novel hybrid multi-epitope vaccine. The epitopes obtained from the selected proteins were screened to ensure their non-allergenicity, non-toxicity, and antigenicity to trigger T and B-cell responses. The interaction of the vaccine with toll-like receptor-3 (TLR-3) and major histocompatibility complexes (MHCs) was assessed using Cluspro 2.0. To establish the reliability of the docked complexes, a comprehensive evaluation was conducted using Immune and MD Simulations and Normal Mode Analysis. However, to validate the computational results of this study, additional in-vitro and in-vivo research is essential.

Follow-Up and Comparative Assessment of SARS-CoV-2 IgA, IgG, Neutralizing, and Total Antibody Responses After BNT162b2 or mRNA-1273 Heterologous Booster Vaccination.

BACKGROUND: Priming with ChAdOx1 followed by heterologous boosting is considered in several countries. Nevertheless, analyses comparing the immunogenicity of heterologous booster to homologous primary vaccination regimens and natural infection are lacking. In this study, we aimed to conduct a comparative assessment of the immunogenicity between homologous primary vaccination regimens and heterologous prime-boost vaccination using BNT162b2 or mRNA-1273. METHODS: We matched vaccinated naïve (VN) individuals (n = 673) with partial vaccination (n = 64), primary vaccination (n = 590), and primary series plus mRNA vaccine heterologous booster (n = 19) with unvaccinated naturally infected (NI) individuals with a documented primary SARS-CoV-2 infection (n = 206). We measured the levels of neutralizing total antibodies (NTAbs), total antibodies (TAbs), anti-S-RBD IgG, and anti-S1 IgA titers. RESULTS: Homologous primary vaccination with ChAdOx1 not only showed less potent NTAb, TAb, anti-S-RBD IgG, and anti-S1 IgA immune responses compared to primary BNT162b2 or mRNA-1273 vaccination regimens (p < 0.05) but also showed ~3-fold less anti-S1 IgA response compared to infection-induced immunity (p < 0.001). Nevertheless, a heterologous booster led to an increase of ~12 times in the immune response when compared to two consecutive homologous ChAdOx1 immunizations. Furthermore, correlation analyses revealed that both anti-S-RBD IgG and anti-S1 IgA significantly contributed to virus neutralization among NI individuals, particularly in symptomatic and pauci-symptomatic individuals, whereas among VN individuals, anti-S-RBD IgG was the main contributor to virus neutralization. CONCLUSION: The results emphasize the potential benefit of using heterologous mRNA boosters to increase antibody levels and neutralizing capacity particularly in patients who received primary vaccination with ChAdOx1.

Characterization and immunogenicity assessment of MERS-CoV pre-fusion spike trimeric oligomers as vaccine immunogen.

Middle East respiratory syndrome coronavirus (MERS-CoV) is a lethal beta-coronavirus that emerged in 2012. The virus is part of the WHO blueprint priority list with a concerning fatality rate of 35%. Scientific efforts are ongoing for the development of vaccines, anti-viral and biotherapeutics, which are majorly directed toward the structural spike protein. However, the ongoing effort is challenging due to conformational instability of the spike protein and the evasion strategy posed by the MERS-CoV. In this study, we have expressed and purified the MERS-CoV pre-fusion spike protein in the Expi293F mammalian expression system. The purified protein was extensively characterized for its biochemical and biophysical properties. Thermal stability analysis showed a melting temperature of 58°C and the protein resisted major structural changes at elevated temperature as revealed by fluorescence spectroscopy and circular dichroism. Immunological assessment of the MERS-CoV spike immunogen in BALB/c mice with AddaVaxTM and Imject alum adjuvants showed elicitation of high titer antibody responses but a more balanced Th1/Th2 response with AddaVaxTM squalene like adjuvant. Together, our results suggest the formation of higher-order trimeric pre-fusion MERS-CoV spike proteins, which were able to induce robust immune responses. The comprehensive characterization of MERS-CoV spike protein warrants a better understanding of MERS spike protein and future vaccine development efforts.

Optimized production of full-length PCV2d virus-like particles in Escherichia coli: A cost-effective and high-yield approach for potential vaccine antigen development.

Porcine circovirus type 2 (PCV2) is a globally prevalent infectious pathogen affecting swine, with its capsid protein (Cap) being the sole structural protein critical for vaccine development. Prior research has demonstrated that PCV2 Cap proteins produced in Escherichia coli (E. coli) can form virus-like particles (VLPs) in vitro, and nuclear localization signal peptides (NLS) play a pivotal role in stabilizing PCV2 VLPs. Recently, PCV2d has emerged as an important strain within the PCV2 epidemic. In this study, we systematically optimized the PCV2d Cap protein and successfully produced intact PCV2d VLPs containing NLS using E. coli. The recombinant PCV2d Cap protein was purified through affinity chromatography, yielding 7.5 mg of recombinant protein per 100 ml of bacterial culture. We augmented the conventional buffer system with various substances such as arginine, ß-mercaptoethanol, glycerol, polyethylene glycol, and glutathione to promote VLP assembly. The recombinant PCV2d Cap self-assembled into VLPs approximately 20 nm in diameter, featuring uniform distribution and exceptional stability in the optimized buffer. We developed the vaccine and immunized pigs and mice, evaluating the immunogenicity of the PCV2d VLPs vaccine by measuring PCV2-IgG, IL-4, TNF-α, and IFN-γ levels, comparing them to commercial vaccines utilizing truncated PCV2 Cap antigens. The HE staining and immunohistochemical tests confirmed that the PCV2 VLPs vaccine offered robust protection. The results revealed that animals vaccinated with the PCV2d VLPs vaccine exhibited high levels of PCV2 antibodies, with TNF-α and IFN-γ levels rapidly increasing at 14 days post-immunization, which were higher than those observed in commercially available vaccines, particularly in the mouse trial. This could be due to the fact that full-length Cap proteins can assemble into more stable PCV2d VLPs in the assembling buffer. In conclusion, our produced PCV2d VLPs vaccine elicited stronger immune responses in pigs and mice compared to commercial vaccines. The PCV2d VLPs from this study serve as an excellent candidate vaccine antigen, providing insights for PCV2d vaccine research.

Humoral immunogenicity assessment after receiving three types of SARS-CoV-2 vaccine.

Several vaccines have been developed against SARS-CoV-2 and subsequently approved by national/international regulators. Detecting specific antibodies after vaccination enables us to evaluate the vaccine's effectiveness. We conducted a prospective longitudinal study among members of Tarbiat Modares University of Tehran, Iran, from 4 September 2021 until 29 December 2021. We aimed to compare the humoral immunogenicity of 3 vaccine types. Participants consisted of 462 adults. Anti-SARS-CoV-2 receptor-binding domain [RBD] IgG titer was compared in 3 groups, each vaccinated by available vaccines in Iran at the time: Oxford/AstraZeneca, COVIran Barekat, and Sinopharm. The median IgG titer was: 91.2, 105.6, 224.0 BAU/ml for Sinopharm, COVIran Barekat and Oxford/AstraZeneca respectively after the first dose; 195.2, 192.0, 337.6 BAU/ml after the second one. We also analyzed the frequency of antibody presence in each vaccine group, in the same order the results were 59.0%, 62.6% and 89.4% after the first dose and 92.1%,89.5% and 98.9% after the second. The comparison of results demonstrated that AstraZeneca vaccine is a superior candidate vaccine for COVID-19 vaccination out of the three. Our data also demonstrated statistically significant higher antibody titer among recipients with an infection history.

Trivalent inactivated influenza vaccine response and immunogenicity assessment after one week and three months in repeatedly vaccinated adults.

BACKGROUND: The influenza vaccine administrated every year is a recommended infection control procedure for individuals above the age of six months. However, the effectiveness of repeated annual vaccination is still an active research topic. Therefore, we investigated the vaccine immunogenicity in two independent groups: previously vaccinated versus non-vaccinated individuals at three time points; prior vaccination, one week and three months post vaccination. The assessment enabled us to evaluate the elicited immune responses and the durability of the induced protection in both groups. RESEARCH DESIGN AND METHODS: A research study was conducted to assess the immunogenicity of a single dose of Trivalent Inactivated Influenza Vaccine (A/H1N1, A/H3N2, and B) in 278 healthy adults aged between 32 and 66 years. Almost half of the participants, 140 (50·36%), received influenza vaccination at least once precursor to past influenza seasons. One blood sample was taken prior to vaccination for complete blood analysis and baseline immunogenicity assessment. The selected study participants received a single vaccine dose on the first day, and then followed up for three months. Two blood samples were taken after one week and three months post vaccination, respectively, for vaccine immunogenicity assessment. RESULTS: Before vaccination, the seroprotection, defined as a hemagglutination-inhibiting titer of =>1:40, was detected for the three vaccine virus strains in 20 previously vaccinated participants (14·29%) [8·95%, 21·2%]. We compared the overall vaccine response for the three virus strains using a normalized response score calculated from linearly transformed titer measurements; the score before vaccination was 84% higher in the previously vaccinated group and the mean difference between the two groups was statistically significant. Three months post-vaccination, we didn't find a significant difference in vaccine responses; the number of fully seroprotected individuals became 48 (34·29%) [26·48%, 42·77%] in the previously vaccinated group and 59 (42·75%) [34·37%, 51·45%] in the non-vaccinated group. The calculated response score was almost equal in both groups and the mean difference was no longer statistically significant. CONCLUSION: Our findings suggest that a single dose of influenza vaccine is equally protective after three months for annually vaccinated adults and first-time vaccine receivers.

A Brighton Collaboration standardized template with key considerations for a benefit/risk assessment for the Novavax COVID-19 Vaccine (NVX-CoV2373), a recombinant spike protein vaccine with Matrix-M adjuvant to prevent disease caused by SARS-CoV-2 viruses.

Novavax, a global vaccine company, began evaluating NVX-CoV2373 in human studies in May 2020 and the pivotal placebo-controlled phase 3 studies started in November 2020; five clinical studies provided adult and adolescent clinical data for over 31,000 participants who were administered NVX-CoV2373. This extensive data has demonstrated a well-tolerated response to NVX-CoV2373 and high vaccine efficacy against mild, moderate, or severe COVID-19 using a two-dose series (Dunkle et al., 2022) [1], (Heath et al., 2021) [2], (Keech et al., 2020) [3], (Mallory et al., 2022) [4]. The most common adverse events seen after administration with NVX-CoV2373 were injection site tenderness, injection site pain, fatigue, myalgia, headache, malaise, arthralgia, nausea, or vomiting. In addition, immunogenicity against variants of interest (VOI) and variants of concern (VOC) was established with high titers of ACE2 receptor-inhibiting and neutralizing antibodies in these studies (EMA, 2022) [5], (FDA, 2023) [6]. Further studies on correlates of protection determined that titers of anti-Spike IgG and neutralizing antibodies correlated with efficacy against symptomatic COVID-19 established in clinical trials (p < 0.001 for recombinant protein vaccine and p = 0.005 for mRNA vaccines for IgG levels) (Fong et al., 2022) [7]. Administration of a booster dose of the recombinant protein vaccine approximately 6 months following the primary two-dose series resulted in substantial increases in humoral antibodies against both the prototype strain and all evaluated variants, similar to or higher than the antibody levels observed in phase 3 studies that were associated with high vaccine efficacy (Dunkle et al., 2022) [1], (Mallory et al., 2022) [4]. These findings, together with the well tolerated safety profile, support use of the recombinant protein vaccine as primary series and booster regimens.

Assessment of mRNA Vaccine Immunogenicity in Solid Organ Transplant Recipients.

Background and Objectives: Solid organ transplant (SOT) recipients have a higher risk of suffering from severe Coronavirus (COVID-19) compared to the general population. Studies have shown impaired immunogenicity of mRNA vaccines in this high-risk population; thus, SOT recipients have been prioritized globally for primary and booster doses. Materials and Methods: We analyzed 144 SOT recipients who had previously received two doses of BNT162b2 or mRNA1273 vaccine, and who were subsequently vaccinated with a booster dose of the mRNA1273 vaccine. Humoral and cellular immune responses were measured 1 and 3 months after the second dose, and 1 month after the third dose. Results: One month after the second dose, 33.6% (45/134) of patients displayed a positive antibody response with a median (25th, 75th) antibody titer of 9 (7, 161) AU/mL. Three months after the second dose, 41.8% (56/134) tested positive with a median (25th, 75th) antibody titer of 18 (7, 251) AU/mL. After the booster dose, the seropositivity rate increased to 69.4% (93/134), with a median (25th, 75th) titer of 966 (10, 8027) AU/mL. The specific SARS-CoV-2 T-cell response was assessed in 44 randomly selected recipients 3 months after the second dose, and 11.4% (5/44) of them had a positive response. Following the third dose, 42% (21/50) tested positive. Side effects after the third dose were mild, with pain at the injection site being the most frequent adverse effect, reported by 73.4% of the recipients. Conclusion: Our study shows a mild delayed increase in antibody titer, three months after primary vaccination compared to one month after. It also shows a robust augmentation of humoral and specific T-cell responses after the booster dose, as well as the safety and tolerability of the mRNA vaccines in SOT recipients.

A Brighton Collaboration standardized template with key considerations for a benefit/risk assessment for the Medigen COVID-19 protein vaccine.

The Brighton Collaboration Benefit-Risk Assessment of VAccines by TechnolOgy (BRAVATO) Working Group has prepared standardized templates to describe the key considerations for the benefit-risk assessment of several vaccine platform technologies, including protein subunit vaccines. This article uses the BRAVATO template to review the features of the MVC-COV1901 vaccine, a recombinant protein subunit vaccine based on the stabilized pre-fusion SARS-CoV-2 spike protein S-2P, adjuvanted with CpG 1018 and aluminum hydroxide, manufactured by Medigen Vaccine Biologics Corporation in Taiwan. MVC-COV1901 vaccine is indicated for active immunization to prevent COVID-19 caused by SARS-CoV-2 in individuals 12 years of age and older. The template offers details on basic vaccine information, target pathogen and population, characteristics of antigen and adjuvant, preclinical data, human safety and efficacy data, and overall benefit-risk assessment. The clinical development program began in September 2020 and based on demonstration of favorable safety and immunogenicity profiles in 11 clinical trials in over 5,000 participants, it has been approved for emergency use based on immunobridging results for adults in Taiwan, Estwatini, Somaliland, and Paraguay. The main clinical trials include placebo-controlled phase 2 studies in healthy adults (CT-COV-21), adolescents (CT-COV-22), and elderly population (CT-COV-23) as well as 3 immunobridging phase 3 trials (CT-COV-31, CT-COV-32, and CT-COV-34) in which MVC-COV1901 was compared to AZD1222. There are also clinical trials studying MVC-COV1901 as homologous and heterologous boosters (CT-COV-24 and CT-COV-25). The totality of evidence based on ∼3 million vaccinees to date includes a mostly clean safety profile, with adverse events mostly being mild and self-limiting in both clinical development and post-marketing experience, proven immunogenic response, and real-world effectiveness data. The immunogenic profile demonstrates that MVC-COV1901 induces high levels of neutralizing and binding antibodies against SARS-CoV-2. There is a dose-dependent response and a significant correlation between binding and neutralizing antibody activity. Antigen-specific T-cell responses, particularly a Th1-biased immune response characterized by high levels of interferon gamma and IL-2 cytokines, have also been observed. Coupled with this, MVC-COV1901 has favorable thermostability and better safety profiles when compared to other authorized vaccines from different platforms, which make it potentially a good candidate for vaccine supply chains in global markets.

Assessment of the influence of ABO blood groups on oral cholera vaccine immunogenicity in a cholera endemic area in Zambia.

BACKGROUND: Histo-blood group antigens (HBGAs) which include the ABO and Lewis antigen systems have been known for determining predisposition to infections. For instance, blood group O individuals have a higher risk of severe illness due to V. cholerae compared to those with non-blood group O antigens. We set out to determine the influence that these HBGAs have on oral cholera vaccine immunogenicity and seroconversion in individuals residing within a cholera endemic area in Zambia. METHODOLOGY: We conducted a longitudinal study nested under a clinical trial in which samples from a cohort of 223 adults who were vaccinated with two doses of Shanchol™ and followed up over 4 years were used. We measured serum vibriocidal geometric mean titers (GMTs) at Baseline, Day 28, Months 6, 12, 24, 30, 36 and 48 in response to the vaccine. Saliva obtained at 1 year post vaccination was tested for HBGA phenotypes and secretor status using an enzyme-linked immunosorbent assay (ELISA). RESULTS: Of the 133/223 participants included in the final analysis, the majority were above 34 years old (58%) and of these, 90% were males. Seroconversion rates to V. cholerae O1 Inaba with non-O (23%) and O (30%) blood types were comparable. The same pattern was observed against O1 Ogawa serotype between non-O (25%) and O (35%). This trend continued over the four-year follow-up period. Similarly, no significant differences were observed in seroconversion rates between the non-secretors (26%) and secretors (36%) against V. cholerae O1 Inaba. The same was observed for O1 Ogawa in non-secretors (22%) and the secretors (36%). CONCLUSION: Our results do not support the idea that ABO blood grouping influence vaccine uptake and responses against cholera.

Immunogenicity of a single 4CMenB vaccine booster in adolescents 11 years after childhood immunisation.

The clinical development of the meningococcal vaccine, 4CMenB, included 2 doses in vaccine-naïve adolescents, which was considered unlikely to be cost-effective for implementation. Theoretically, priming with 4CMenB in early childhood might drive strong immune responses after only a single booster dose in adolescents and reduce programmatic costs. To address this question, children over 11 years old who took part in previous trials involving the administration of 3-5 doses of 4CMenB at infant/preschool age from 2006 were recruited into a post licensure single-centre trial, and were divided into two groups: those who received their last dose at 12 months old (infant group) and those who received their last dose at 3 years old (infant + preschool group). Naïve age-matched controls were randomised to receive one (adolescent 1 group) or two doses at days 0 and 28 (adolescent 2 group) of 4CMenB. Serum bactericidal antibody (SBA) assays using human complement were performed against three reference strains prior to vaccination, and at 1, 6 and 12 months. Previous vaccination was associated with a higher response to a single booster dose at 11 years of age, one-month post-vaccination, when compared with a single dose in naïve age-matched controls. At day 180, the highest responses were observed in participants in the infant + preschool group against strain 5/99 (GMT 316.1 [CI 158.4 to 630.8]), as compared with naïve adolescents who received two doses (GMTs 84.5 [CI 57.7 to 123.6]). When the last dose was received at 12-months of age, responses to a single adolescent dose were not as robust (GMT 61.1 [CI 14.8 to 252.4] to strain 5/99). This descriptive study indicates that the highest SBA responses after a single dose in adolescence were observed in participants who received a preschool dose, suggesting that B cell memory responses are not sufficiently primed at less than 12 months of age. Trial registration EudraCT 2017-004732-11, ISRCTN16774163.

Early assessment of the safety and immunogenicity of a third dose (booster) of COVID-19 immunization in Chinese adults.

Inducing durable and effective immunity against severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) via vaccination is essential to combat the current pandemic of coronavirus disease 2019 (COVID-19). It has been noticed that the strength of anti-COVID-19 vaccination-induced immunity fades over time, which calls for an additional vaccination regime, as known as booster immunization, to restore immunity among previously vaccinated populations. Here we report a pilot open-label trial of a third dose of BBIBP-CorV, an inactivated SARS-CoV-2 vaccine (Vero cell), on 136 participants aged between 18 to 63 years. Safety and immunogenicity in terms of neutralizing antibody titers and cytokine/chemokine responses were analyzed as the main endpoint until day 28. While systemic reactogenicity was either absent or mild, SARS-CoV-2-specific neutralizing antibody titers rapidly arose in all participants within 4 weeks, surpassing the peak antibody titers elicited by the initial two-dose immunization regime. Broad increases of cellular immunity-associated cytokines and chemokines were also detected in the majority of participants after the third vaccination. Furthermore, in an exploratory study, a newly developed recombinant protein vaccine, NVSI-06-08 (CHO Cells), was found to be safe and even more effective than BBIBP-CorV in eliciting humoral immune responses in BBIBP-CorV-primed individuals. Together, these results indicate that a third immunization schedule with either homologous or heterologous vaccine showed favorable safety profiles and restored potent SARS-CoV-2-specific immunity, providing support for further trials of booster vaccination in larger populations.

Qualitative assessment of anti-SARS-CoV-2 spike protein immunogenicity (QUASI) after COVID-19 vaccination in older people living with HIV.

OBJECTIVES: Effective and safe COVID-19 vaccines have been developed and have resulted in decreased incidence and severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and can decrease secondary transmission. However, there are concerns about dampened immune responses to COVID-19 vaccination among immunocompromised patients, including people living with HIV (PLWH), which may blunt the vaccine's efficacy and durability of protection. This study aimed to assess the qualitative SARS-CoV-2 vaccine immunogenicity among PLWH after vaccination. METHODS: We conducted targeted COVID-19 vaccination (all received BNT162b2 vaccine) of PLWH (aged ≥ 55 years per state guidelines) at Yale New Haven Health System and established a longitudinal survey to assess their qualitative antibody responses at 3 weeks after the first vaccination (and prior to receipt of the second dose of the COVID-19 vaccine) (visit 1) and at 2-3 weeks after the second vaccination (visit 2) but excluded patients with prior COVID-19 infection. Our goal was to assess vaccine-induced immunity in the population we studied. Qualitative immunogenicity testing was performed using Healgen COVID-19 anti-Spike IgG/IgM rapid testing. Poisson regression with robust standard errors was used to determine factors associated with a positive IgG response. RESULTS: At visit 1, 45 of 78 subjects (57.7%) tested positive for SARS-CoV-2 anti-Spike IgG after the first dose of COVID-19 vaccine. Thirty-nine subjects returned for visit 2. Of these, 38 had positive IgG (97.5%), including 20 of 21 subjects (95.2%) with an initial negative anti-Spike IgG. Our bivariate analysis suggested that participants on an antiretroviral regimen containing integrase strand transfer inhibitors [relative risk (RR) = 1.81, 95% confidence interval (CI): 0.92-3.56, p = 0.085] were more likely to seroconvert after the first dose of the COVID-19 vaccine, while those with a CD4 count < 500 cells/µL (RR = 0.59, 95% CI: 0.33-1.05, p = 0.071), and those diagnosed with cancer or another immunosuppressive condition (RR = 0.49, 95% CI: 0.18-1.28, p = 0.15) may have been less likely to seroconvert after the first dose of the COVID-19 vaccine. The direction of these associations was similar in the multivariate model, although none of these findings reached statistical significance (RRintegrase inhibitor  = 1.71, 95% CI: 0.90-3.25, p = 0.10; RRCD4 count  = 0.68, 95% CI: 0.39-1.19, p = 0.18; RRcancer or another immunosuppressive condition  = 0.50, 95% CI: 0.19-1.33, p = 0.16). With regard to immunogenicity, we were able to record very high rates of new seroconversion following the second dose of the COVID-19 vaccine. CONCLUSIONS: Our study suggests that completing a two-dose series of BNT162b2 vaccine is critical for PLWH given suboptimal seroconversion rates after the first dose and subsequent improved seroconversion rates after the second dose.

Early clinical trial data and real-world assessment of COVID-19 vaccines: Insights from the Society of Infectious Diseases Pharmacists.

As of August 2021, there were three COVID-19 vaccines available in the United States for the prevention of coronavirus 2019 (COVID-19). The purpose of this narrative review is to examine the early experience from the Emergency Use Authorization (EUA) of BNT162b2 (Pfizer, Inc./BioNTech), mRNA-1273 (Moderna, Inc.), and Ad26.COV2.S (Johnson and Johnson/Janssen Global Services, LLC) through July 2021. The EUA data from the clinical trials have largely been corroborated by real-world effectiveness investigations post-authorization. These studies indicate that immunity is obtained within 2 weeks post-vaccination and may endure for 6 months. The immunity conferred by the vaccines may also be effective against SARS-CoV-2 variants of concern. Additionally, populations not included in the emergency use authorization studies may also benefit from vaccination. This look back at the initial clinical experience can be used by the global community to inform and develop COVID-19 vaccine programs.

Promising Technologies in the Field of Helminth Vaccines.

Helminths contribute a larger global burden of disease than both malaria and tuberculosis. These eukaryotes have caused human infections since before our earliest recorded history (i.e.: earlier than 1200 B.C. for Schistosoma spp.). Despite the prevalence and importance of these infections, helminths are considered a neglected tropical disease for which there are no vaccines approved for human use. Similar to other parasites, helminths are complex organisms which employ a plethora of features such as: complex life cycles, chronic infections, and antigenic mimicry to name a few, making them difficult to target by conventional vaccine strategies. With novel vaccine strategies such as viral vectors and genetic elements, numerous constructs are being defined for a wide range of helminth parasites; however, it has yet to be discussed which of these approaches may be the most effective. With human trials being conducted, and a pipeline of potential anti-helminthic antigens, greater understanding of helminth vaccine-induced immunity is necessary for the development of potent vaccine platforms and their optimal design. This review outlines the conventional and the most promising approaches in clinical and preclinical helminth vaccinology.

Immunogenicity and safety of different schedules of the meningococcal ABCWY vaccine, with assessment of long-term antibody persistence and booster responses - results from two phase 2b randomized trials in adolescents.

The meningococcal serogroup B (MenB) protein vaccine, 4CMenB, combined with MenA, MenC, MenW and MenY polysaccharide-protein conjugates for a pentavalent MenABCWY vaccine, can potentially protect against most causative agents of invasive meningococcal disease worldwide. Two phase 2b, randomized, multicenter studies were conducted (NCT02212457, NCT02946385) to assess the immunogenicity and safety of the MenABCWY vaccine as well as antibody persistence and response to a booster dose 2 years after the last vaccination, compared to 4CMenB vaccination. Participants (10 - 18 years), randomized (3:3:2:2:2:2), received the 4-component 4CMenB vaccine according to a 0-2 month (M) schedule or MenABCWY according to a 0-2, 0-6, 0-2-6, 0-1, or 0-11 M schedule. All participants received 5 injections (at M0, M1, M2, M6 and M12) with either the study vaccines or placebo/hepatitis A vaccine. Follow-on participants (4CMenB-0-2, MenABCWY-0-2, MenABCWY-0-6 and MenABCWY-0-2-6 groups) received one dose of either 4CMenB (4CMenB-0-2 group) or MenABCWY and newly enrolled, age-matched, meningococcal vaccine-naïve adolescents (randomized 1:1) received 2 doses (0-2 M) of either 4CMenB or MenABCWY. MenABCWY vaccination was immunogenic against MenB test strains. Non-inferiority for all 4 components of the 4CMenB vaccine could not be demonstrated for the 0-2 M schedule. Antibodies persisted up to 2 years post-MenABCWY vaccination and a booster dose induced an anamnestic response as higher titers were observed in follow-on participants compared to the first-dose response in vaccine-naïve participants. MenABCWY had a clinically-acceptable safety profile, not different from that of 4CMenB.

Engineered SARS-CoV-2 receptor binding domain improves manufacturability in yeast and immunogenicity in mice.

Global containment of COVID-19 still requires accessible and affordable vaccines for low- and middle-income countries (LMICs). Recently approved vaccines provide needed interventions, albeit at prices that may limit their global access. Subunit vaccines based on recombinant proteins are suited for large-volume microbial manufacturing to yield billions of doses annually, minimizing their manufacturing cost. These types of vaccines are well-established, proven interventions with multiple safe and efficacious commercial examples. Many vaccine candidates of this type for SARS-CoV-2 rely on sequences containing the receptor-binding domain (RBD), which mediates viral entry to cells via ACE2. Here we report an engineered sequence variant of RBD that exhibits high-yield manufacturability, high-affinity binding to ACE2, and enhanced immunogenicity after a single dose in mice compared to the Wuhan-Hu-1 variant used in current vaccines. Antibodies raised against the engineered protein exhibited heterotypic binding to the RBD from two recently reported SARS-CoV-2 variants of concern (501Y.V1/V2). Presentation of the engineered RBD on a designed virus-like particle (VLP) also reduced weight loss in hamsters upon viral challenge.