Development of an effective immune response in adults with Down Syndrome after SARS-CoV-2 vaccination

Immune dysregulation in individuals with Down syndrome (DS) leads to an increased risk for hospitalization and death due to COVID-19 and may impair the generation of protective immunity after vaccine administration. The cellular and humoral responses of 55 DS patients who received a complete SARS-CoV-2 vaccination regime at one to three (V1) and six (V2) months were characterised. SARS-CoV-2-reactive CD4+ and CD8+ T lymphocytes with a predominant Th1 phenotype were observed at V1, and increased at V2. Likewise, a sustained increase of SARS-CoV-2-specific circulating Tfh (cTfh) cells was observed one to three months after vaccine administration. Specific IgG antibodies against SARS-CoV-2 S protein were detected in 96% and 98% of subjects at V1 and V2, respectively, though IgG titers decreased significantly between both timepoints.

Immune Responses and Protective Immunity in Pangasius Pangasius (Hamilton, 1822) as Induced by Outer Membrane Proteins of Edwardsiella Tarda and Aluminium Hydroxide Adjuvant Complex

Edwardsiella tarda is considered one of the important bacterial fish pathogens. The outer membrane proteins (OMPs) of E. tarda are structurally and functionally conserved, and immunogenic. This study assessed the effects of the OMPs of E. tarda CGH9 as a vaccine without aluminium hydroxide [AH] (T1) and with AH adjuvant (T2) on the respiratory burst (ROB) activity, lymphocyte proliferation of head kidney (HK) leukocytes, and serum antibody production in pangas catfish Pangasius pangasius. The ROB activity and lymphocyte proliferation of HK leukocytes increased in both vaccinated groups compared to control. Nonetheless, the T2 group showed a gradual increase in ROB activity and lymphocyte proliferation of HK leukocytes up to 3-weeks post-vaccination (wpv). The serum antibody production in the T1 group decreased initially for up to 2-wpv and increased from 3-wpv; whereas, in the T2 group, the serum-specific antibody levels were significantly high from 1-wpv compared to control. Simultaneously, the protective efficacy in terms of relative percentage survival (RPS) in the T2 group after injecting with a lethal dose of E. tarda CGH9 was high (89.00±15.56) compared to the T1 group (78.00±0.00). Furthermore, the catfish administered with a booster dose of E. tarda OMPs with or without AH adjuvant showed no additional increase in immune response or protective immunity. These results suggested that E. tarda OMPs and AH adjuvant complex has a higher potential to induce protective immunity, which may be a good choice as a vaccine to combat E. tarda infection in catfish.

Identification, Mapping, and Genetic Diversity of Novel Conserved Cross-Species Epitopes of RhopH2 in Plasmodium knowlesi With Plasmodium vivax

Malaria is a major public health concern, and any tangible intervention during the pre-elimination phase can result in a significant reduction in infection rates. Recent studies have reported that antigens producing cross-protective immunity can play an important role as vaccines and halt malaria transmission in different endemic regions. In this study, we studied the genetic diversity, natural selection, and discovered novel conserved epitopes of a high molecular weight rhoptry protein 2 (RhopH2) in clinical samples of Plasmodium knowlesi and Plasmodium vivax cross-protective domains, which has been proven to produce cross-protective immunity in both species. We found low levels of nucleotide diversity (P. knowlesi; π ~ 0.0093, SNPs = 49 and P. vivax π ~ 0.0014, SNPs = 23) in P. knowlesi (n = 40) and P. vivax (n = 65) samples in the PkRhopH2 cross-protective domain. Strong purifying selection was observed for both species (P. knowlesi; dS - dN = 2.41, p < 0.009, P. vivax; dS - dN = 1.58, p < 0.050). In silico epitope prediction in P. knowlesi identified 10 potential epitopes, of which 7 epitopes were 100% conserved within clinical samples. Of these epitopes, an epitope with 10 amino acids (QNSKHFKKEK) was found to be fully conserved within all P. knowlesi and P. vivax clinical samples and 80%–90% conservation within simian malaria ortholog species, i.e., P. coatneyi and P. cynomolgi. Phylogenetic analysis of the PkRhopH2 cross-protective domain showed geographical clustering, and three subpopulations of P. knowlesi were identified of which two subpopulations originated from Sarawak, Malaysian Borneo, and one comprised only the laboratory lines from Peninsular Malaysia. This study suggests that RhopH2 could be an excellent target for cross-protective vaccine development with potential for outwitting strain as well as species-specific immunity. However, more detailed studies on genetic diversity using more clinical samples from both species as well as the functional role of antibodies specific to the novel conserved epitope identified in this study can be explored for protection against infection.

Immunity to Sda1 Protects against Infection by Sda1+ and Sda1− Serotypes of Group A Streptococcus

Group A Streptococcus (GAS) causes a variety of diseases globally. The DNases in GAS promote GAS evasion of neutrophil killing by degrading neutrophil extracellular traps (NETs). Sda1 is a prophage-encoded DNase associated with virulent GAS strains. However, protective immunity against Sda1 has not been determined. In this study, we explored the potential of Sda1 as a vaccine candidate. Sda1 was used as a vaccine to immunize mice intranasally. The effect of anti-Sda1 IgG in neutralizing degradation of NETs was determined and the protective role of Sda1 was investigated with intranasal and systemic challenge models. Antigen-specific antibodies were induced in the sera and pharyngeal mucosal site after Sda1 immunization. The anti-Sda1 IgG efficiently prevented degradation of NETs by supernatant samples from different GAS serotypes with or without Sda1. Sda1 immunization promoted clearance of GAS from the nasopharynx independent of GAS serotypes but did not reduce lethality after systemic GAS challenge. Anti-Sda1 antibody can neutralize degradation of NETs by Sda1 and other phage-encoded DNases and decrease GAS colonization at the nasopharynx across serotypes. These results indicate that Sda1 can be a potential vaccine candidate for reduction in GAS reservoir and GAS tonsillitis-associated diseases.

The Chimeric Binjari-Zika Vaccine Provides Long-Term Protection against ZIKA Virus Challenge

We recently developed a chimeric flavivirus vaccine technology based on the novel insect-specific Binjari virus (BinJV) and used this to generate a chimeric ZIKV vaccine (BinJ/ZIKA-prME) that protected IFNAR-/- dams and fetuses from infection. Herein, we show that a single vaccination of IFNAR-/- mice with unadjuvanted BinJ/ZIKA-prME generated neutralizing antibody responses that were retained for 14 months. At 15 months post vaccination, mice were also completely protected against detectable viremia and substantial body weight loss after challenge with ZIKVPRVABC59. BinJ/ZIKA-prME vaccination thus provided long-term protective immunity without the need for adjuvant or replication of the vaccine in the vaccine recipient, both attractive features for a ZIKV vaccine.

Neutralizing antibody titres to SARS-CoV-2 Omicron variant and wild-type virus in those with past infection or vaccinated or boosted with mRNA BNT162b2 or inactivated CoronaVac vaccines

Omicron, a novel SARS-CoV-2 variant has emerged and is rapidly becoming the dominant SARS-CoV-2 virus circulating globally. It is important to define reductions in virus neutralizing activity in serum of convalescent or vaccinated individuals to understand potential loss of protection from infection or re-infection. Two doses of BNT162b2 or CoronaVac vaccines provided little 50% plaque reduction neutralization test (PRNT50) antibody immunity against the Omicron variant, even at one-month post vaccination. Booster doses with BNT162b2 in those with two doses of either BNT162b2 or CoronaVac provided acceptable neutralizing immunity against Omicron variant at 1-month post-booster dose. However, three doses of BNT162b2 elicited higher levels of PRNT50 antibody to Omicron variant suggesting longer duration of protection. Convalescent from SARS-CoV-2 infection did not have protective PRNT50 antibody levels to Omicron, but a single dose of BNT162b2 vaccine provided protective immunity. Field vaccine-efficacy studies against Omicron variant against different vaccines are urgently needed.

Incidence of COVID-19 reinfection among Midwestern healthcare employees

Given the overwhelming worldwide rate of infection and the disappointing pace of vaccination, addressing reinfection is critical. Understanding reinfection, including longevity after natural infection, will allow us to better know the prospect of herd immunity, which hinges on the assumption that natural infection generates sufficient, protective immunity. The primary objective of this observational cohort study is to establish the incidence of reinfection of COVID-19 among healthcare employees who experienced a prior COVID-19 infection over a 10-month period. Of 2,625 participants who experienced at least one COVID-19 infection during the 10-month study period, 156 (5.94%) experienced reinfection and 540 (20.57%) experienced recurrence after prior infection. Median days were 126.50 (105.50–171.00) to reinfection and 31.50 (10.00–72.00) to recurrence. Incidence rate of COVID-19 reinfection was 0.35 cases per 1,000 person-days, with participants working in COVID-clinical and clinical units experiencing 3.77 and 3.57 times, respectively, greater risk of reinfection relative to those working in non-clinical units. Incidence rate of COVID-19 recurrence was 1.47 cases per 1,000 person-days. This study supports the consensus that COVID-19 reinfection, defined as subsequent infection ≥ 90 days after prior infection, is rare, even among a sample of healthcare workers with frequent exposure.

Protective immunity induced by oral vaccination with a recombinant Lactococcus lactis vaccine against H5Nx in chickens

Background The development of an influenza vaccine for poultry that provides broadly protective immunity against influenza H5Nx viruses is a challenging goal. Results Lactococcus lactis (L. lactis)/pNZ8149-HA1-M2 expressing hemagglutinin-1 (HA1) of A/chicken/Vietnam/NCVD-15A59/2015 (H5N6) and the conserved M2 gene of A/Vietnam/1203/2004 (H5N1) was generated. L. lactis/pNZ8149-HA1-M2 could induce significant humoral, mucosal and cell-mediated immune responses, as well as neutralization antibodies. Importantly, L. lactis/pNZ8149-HA1-M2 could prevent disease symptoms without significant weight loss and confer protective immunity in a chicken model against lethal challenge with divergent influenza H5Nx viruses, including H5N6 and H5N1. Conclusions L. lactis/pNZ8149-HA1-M2 can serve as a promising vaccine candidate in poultry industry for providing protection against H5Nx virus infection in the field application.