scholarly journals Broad neutralization against SARS-CoV-2 variants induced by a modified B.1.351 protein-based COVID-19 vaccine candidate

2021 ◽  
Author(s):  
Danmei Su ◽  
Xinglin Li ◽  
Cui He ◽  
Xueqin Huang ◽  
Meilin Chen ◽  
...  

Beginning in late 2020, the emergence and spread of multiple variant SARS-CoV-2 strains harboring mutations which may enable immune escape necessitates the rapid evaluation of second generation COVID-19 vaccines, with the goal of inducing optimized immune responses that are broadly protective. Here we demonstrate in a mouse immunogenicity study that two doses of a modified B.1.351 spike (S)-Trimer vaccine (B.1.351 S-Trimer) candidate can induce strong humoral immune responses that can broadly neutralize both the original SARS-CoV-2 strain (Wuhan-Hu-1) and Variants of Concern (VOCs), including the UK variant (B.1.1.7), South African variant (B.1.351) and Brazil variant (P.1). Furthermore, while immunization with two doses (prime-boost) of Prototype S-Trimer vaccine (based on the original SARS-CoV-2 strain) induced lower levels of cross-reactive neutralization against the B.1.351 variant, a third dose (booster) administered with either Prototype S-Trimer or B.1.351 S-Trimer was able to increase neutralizing antibody titers against B.1.351 to levels comparable to neutralizing antibody titers against the original strain elicited by two doses of Prototype S-Trimer.

2021 ◽  
Author(s):  
Preethi Eldi ◽  
Tamara H Cooper ◽  
Natalie A Prow ◽  
Liang Liu ◽  
Gary K Heinemann ◽  
...  

The ongoing COVID-19 pandemic perpetuated by SARS-CoV-2 variants, has highlighted the continued need for broadly protective vaccines that elicit robust and durable protection. Here, the vaccinia virus-based, replication-defective Sementis Copenhagen Vector (SCV) was used to develop a first-generation COVID-19 vaccine encoding the spike glycoprotein (SCV-S). Vaccination of mice rapidly induced polyfunctional CD8 T cells with cytotoxic activity and robust Th1-biased, spike-specific neutralizing antibodies, which are significantly increased following a second vaccination, and contained neutralizing activity against the alpha and beta variants of concern. Longitudinal studies indicated neutralizing antibody activity was maintained up to 9 months post-vaccination in both young and aging mice, with durable immune memory evident even in the presence of pre-existing vector immunity. This immunogenicity profile suggests a potential to expand protection generated by current vaccines in a heterologous boost format, and presents a solid basis for second-generation SCV-based COVID-19 vaccine candidates incorporating additional SARS-CoV-2 immunogens.


Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 729
Author(s):  
Leah E. Cole ◽  
Jinrong Zhang ◽  
Kristl M. Pacheco ◽  
Philippe Lhéritier ◽  
Natalie G. Anosova ◽  
...  

While both whole-cell (wP) and acellular pertussis (aP) vaccines have been highly effective at reducing the global pertussis disease burden, there are concerns that compared to wP vaccination, the immune responses to aP vaccination may wane more rapidly. To gain insights into the vaccine elicited immune responses, pre-adult baboons were immunized with either aP or wP vaccines, boosted with an aP vaccine, and observed over a nearly two-year period. Priming with a wP vaccine elicited a more Th17-biased response than priming with aP, whereas priming with an aP vaccine led to a more Th2-biased response than priming with wP. These differences were maintained after aP vaccine boost immunizations. Compared to aP, animals primed with a wP vaccine exhibited greater numbers of pertussis specific memory B cells. While aP and wP vaccine priming initially elicited similar levels of anti-pertussis toxin antibody, titers declined more rapidly in aP vaccine primed animals leading to a 4-fold difference. Both wP and aP vaccine immunization could induce serum bactericidal activity (SBA); however, only one wP vaccine immunization was required to elicit SBA while multiple aP vaccine immunizations were required to elicit lower, less durable SBA titers. In conclusion, when compared to aP vaccine, priming with wP vaccine elicits distinct cellular and humoral immune responses that persist after aP vaccine boosting.


Author(s):  
M.C. Oliveira ◽  
D.F. Figueiredo-Lima ◽  
D.E. Faria Filho ◽  
R.H. Marques ◽  
V.M.B. Moraes

The effect of including mannanoligosaccharides (MOS) and/or enzymes in broiler diets on antibody titers against infectious bursal disease virus (IBDV) and Newcastle disease virus (NDV) was evaluated. A total of 750 broilers were distributed into a completely randomized experimental design in a factorial arrangement 2 x 2 + 1 with two levels of MOS (0 and 0.1% until 21 days and 0.05% from 22 to 42 days of age), two levels of enzymes (0 and 0.05%) and a positive control diet containing antibiotic, totaling five treatments with five replicates each. For antibody analyses, blood samples were weekly collected by jugular vein puncture in the same two birds per replicate. The first and last collections were done at 7 and 42 days of age, respectively. The inclusion of MOS resulted in increased antibody titers against IBDV in the fourth (P<0.03) and fifth (P<0.02) weeks, and against NDV in the third (P<0.01), fourth (P<0.03) and fifth (P<0.03) weeks of age. MOS was effective in stimulating the humoral immune responses against IBDV and NDV vaccine viruses.


Blood ◽  
2009 ◽  
Vol 113 (18) ◽  
pp. 4250-4261 ◽  
Author(s):  
Thaidra Gaufin ◽  
Rajeev Gautam ◽  
Melissa Kasheta ◽  
Ruy Ribeiro ◽  
Erin Ribka ◽  
...  

AbstractWe investigated the impact of rhesus macaque (RM) B-cell depletion before inoculation with the isolate SIVsmmD215. Seven RMs were treated every 3 weeks with 50 mg/kg of an anti-CD20 antibody (rituximab) starting 7 days before inoculation for 2 (n = 4) and 5 (n = 3) months. Four control animals received no antibody. Three animals were completely depleted of CD20+ B cells, but 4 were only partially depleted of CD20 cells in the LNs and intestine. The decrease in antibody production was consistent with the efficacy of tissue CD20 depletion. Seroconversion and neutralizing antibody production was significantly delayed in animals showing complete tissue CD20 depletion and remained at low titers in all CD20-depleted RMs. Surprisingly, there was no significant difference in acute or chronic viral loads between CD20-depleted and control animal groups. There was a tendency for lower viral set points in CD20-depleted animals. At 6 weeks after inoculation, cellular immune responses were significantly stronger in CD20-depleted animals than in controls. There was no significant difference in survival between CD20-depleted and control animals. Our data suggest that a deficiency of Ab responses did not markedly affect viral replication or disease progression and that they may be compensated by more robust cellular responses.


2006 ◽  
Vol 203 (3) ◽  
pp. 529-539 ◽  
Author(s):  
Rika Draenert ◽  
Todd M. Allen ◽  
Yang Liu ◽  
Terri Wrin ◽  
Colombe Chappey ◽  
...  

The predictability of virus–host interactions and disease progression in rapidly evolving human viral infections has been difficult to assess because of host and genetic viral diversity. Here we examined adaptive HIV-specific cellular and humoral immune responses and viral evolution in adult monozygotic twins simultaneously infected with the same virus. CD4 T cell counts and viral loads followed similar trajectories over three years of follow up. The initial CD8 T cell response targeted 17 epitopes, 15 of which were identical in each twin, including two immunodominant responses. By 36 months after infection, 14 of 15 initial responses were still detectable in both, whereas all new responses were subdominant and remained so. Of four responses that declined in both twins, three demonstrated mutations at the same residue. In addition, the evolving antibody responses cross-neutralized the other twin's virus, with similar changes in the pattern of evolution in the envelope gene. These results reveal considerable concordance of adaptive cellular and humoral immune responses and HIV evolution in the same genetic environment, suggesting constraints on mutational pathways to HIV immune escape.


2021 ◽  
Vol 96 ◽  
pp. 107599
Author(s):  
Mohammad Ali Savoji ◽  
Mohammad Mehdi Adibzadeh Sereshgi ◽  
Seyed Mohammad Mahdi Ghahari ◽  
Fatemeh Asgarhalvaei ◽  
Mehdi Mahdavi

2021 ◽  
Vol 12 ◽  
Author(s):  
Eliott Lafon ◽  
Gabriel Diem ◽  
Christina Witting ◽  
Viktoria Zaderer ◽  
Rosa Maria Bellmann-Weiler ◽  
...  

T cells play a fundamental role in the early control and clearance of many viral infections of the respiratory system. In SARS-CoV-2-infected individuals, lymphopenia with drastically reduced CD4+ and CD8+ T cells correlates with Coronavirus disease 2019 (COVID-19)-associated disease severity and mortality. In this study, we characterized cellular and humoral immune responses induced in patients with mild, severe and critical COVID-19. Peripheral blood mononuclear cells of 37 patients with mild, severe and critical COVID-19 and 10 healthy individuals were analyzed by IFNγ ELISpot and multi-color flow cytometry upon stimulation with peptide pools covering complete immunodominant SARS-CoV-2 matrix, nucleocapsid and spike proteins. In addition SARS-CoV-2 antibody levels, neutralization abilities and anaphylatoxin levels were evaluated by various commercially available ELISA platforms. Our data clearly demonstrates a significantly stronger induction of SARS-CoV-2 specific CD8+ T lymphocytes and higher IFNγ production in patients with mild compared to patients with severe or critical COVID-19. In all patients SARS-CoV-2-specific antibodies with similar neutralizing activity were detected, but highest titers of total IgGs were observed in critical patients. Finally, elevated anaphylatoxin C3a and C5a levels were identified in severe and critical COVID-19 patients probably caused by aberrant immune complex formation due to elevated antibody titers in these patients. Crucially, we provide a full picture of cellular and humoral immune responses of COVID-19 patients and prove that robust polyfunctional CD8+ T cell responses concomitant with low anaphylatoxin levels correlate with mild infections. In addition, our data indicates that high SARS-CoV-2 antibody titers are associated with severe disease progression.


2013 ◽  
Vol 56 (1) ◽  
pp. 842-850 ◽  
Author(s):  
M. M. Saei ◽  
A. A. Sadeghi ◽  
H. Ahmadvand

Abstract. A study was conducted to investigate the capability of Myrtus communis essential oil (MCE) in counteracting the deleterious effects of aflatoxin B1 (AFB1) on growth performance, serum biochemistry and humoral immune responses in broiler chickens. In a completely randomized design, 300 day-old male chicks were assigned to four treatments with five replicates of 15 birds for 42 days. Chickens, up to day 7 of age, were fed the same diet and then, they were fed the experimental diets. The dietary treatments were 1) the negative control (no dietary aflatoxin or MCE), 2) the positive control (diet containing AFB1 at 0.5 mg/kg, without MCE), 3) diet containing AFB1 at 0.5 mg/kg plus 500 mg/kg MCE, and 4) basal diet containing 500 mg/kg MCE, without AFB1. Growth performance was measured from day 7 to 42. Serum biochemical parameters, organ weights on day 42 and the antibody titers against Newcastle and influenza viruses on day 28 of age were determined. Addition of aflatoxin to diet decreased (P<0.05) the weight gain and feed intake and MCE supplementation diminished (P<0.05) the inhibitory effects of AFB1 on the growth performance. Addition of AFB1 to diet of chicks increased the serum activities of aspartate aminotransferase (AST), alkaline aminotransferase (ALT), alkaline phosphatase (ALP), and decreased the antibody titers against Newcastle and influenza viruses. Addition of MCE to diet alleviated the negative effects of AFB1 on these parameters (P<0.05). In conclusion, our results showed that addition of MCE may reduce the adverse effects of AFB1 on broiler chickens.


2021 ◽  
Author(s):  
Carolina Garrido ◽  
Jillian H Hurst ◽  
Cynthia G. Lorang ◽  
Jhoanna N. Aquino ◽  
Javier Rodriguez ◽  
...  

As SARS-CoV-2 continues to spread globally, questions have emerged regarding the strength and durability of immune responses in specific populations. In this study, we evaluated humoral immune responses in 69 children and adolescents with asymptomatic or mild symptomatic SARS-CoV-2 infection. We detected robust IgM, IgG, and IgA antibody responses to a broad array of SARS-CoV-2 antigens at the time of acute infection and 2 and 4 months after acute infection in all participants. Notably, these antibody responses were associated with virus neutralizing activity that was still detectable 4 months after acute infection in 94% of children. Moreover, antibody responses and neutralizing activity in sera from children and adolescents were comparable or superior to those observed in sera from 24 adults with mild symptomatic infection. Taken together, these findings indicate children and adolescents with mild or asymptomatic SARS-CoV-2 infection generate robust and durable humoral immune responses that are likely to protect from reinfection.


2021 ◽  
Author(s):  
Mark A. Brockman ◽  
Francis M. Mwimanzi ◽  
Hope R. Lapointe ◽  
Yurou Sang ◽  
Olga Agafitei ◽  
...  

Background mRNA vaccines reduce COVID-19 incidence and severity, but the durability of vaccine-induced immune responses, particularly among the elderly, remains incompletely characterized. Methods Anti-spike RBD antibody titers, ACE2 competition and virus neutralizing activities were longitudinally assessed in 151 healthcare workers and older adults (overall aged 24-98 years) up to three months after vaccination. Results Older adults exhibited lower antibody responses after one and two vaccine doses for all measures. In multivariable analyses correcting for sociodemographic, chronic health and vaccine-related variables, age remained independently associated with all response outcomes. The number of chronic health conditions was additionally associated with lower binding antibody responses after two doses, and male sex with lower ACE2 competition activity after one dose. Responses waned universally at three months after the second dose, but binding antibodies, ACE2 competition and neutralizing activities remained significantly lower with age. Older adults also displayed reduced ability to block ACE2 binding by the Delta variant. Conclusions The humoral immune response to COVID-19 mRNA vaccines is significantly weaker with age, and universally wanes over time. This will likely reduce antibody-mediated protection against SARS-CoV-2 and the Delta variant as the pandemic progresses. Older adults may benefit from additional immunizations as a priority.


Sign in / Sign up

Export Citation Format

Share Document