scholarly journals Are COVID-19 Vaccine Boosters Needed? The Science behind Boosters

2021 ◽  
Author(s):  
Rachel M. Burckhardt ◽  
John J. Dennehy ◽  
Leo L. M. Poon ◽  
Linda J. Saif ◽  
Lynn W. Enquist
Keyword(s):  
Herd Immunity ◽  
Neutralizing Antibody ◽  
Global Pandemic ◽  
Vaccine Booster ◽  
Vaccine Distribution ◽  
Antibody Levels ◽  
Induced Immunity

Waning vaccine-induced immunity coupled with the emergence of SARS-CoV-2 variants has led to increases in breakthrough infections, prompting consideration for vaccine booster doses. Boosters have been reported to be safe and increase SARS-CoV-2-specific neutralizing antibody levels, but how these doses impact the trajectory of the global pandemic and herd immunity is unknown. Information on immunology, epidemiology and equitable vaccine distribution should be considered when deciding the timing and eligibility for COVID-19 vaccine boosters.

scholarly journals Choosing the right tool for the job: A comprehensive assessment of serological assays for SARS-CoV-2 as surrogates for authentic virus neutralization

2021 ◽  
Author(s):  
Nicholas Wohlgemuth ◽  
Kendall Whitt ◽  
Sean Cherry ◽  
Ericka Kirkpatrick Roubidoux ◽  
Chun-Yang Lin ◽  
...  
Keyword(s):  
Neutralizing Antibody ◽  
Virus Neutralization ◽  
Diagnostic Tools ◽  
Pseudotyped Virus ◽  
Global Pandemic ◽  
Level 3 ◽  
The Right ◽  
Antibody Levels ◽  
Reliable Methods ◽  
Biosafety Level

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019 and has since caused a global pandemic resulting in millions of cases and deaths. Diagnostic tools and serological assays are critical for controlling the outbreak, especially assays designed to quantitate neutralizing antibody levels, considered the best correlate of protection. As vaccines become increasingly available, it is important to identify reliable methods for measuring neutralizing antibody responses that correlate with authentic virus neutralization but can be performed outside of biosafety level 3 (BSL3) laboratories. While many neutralizing assays using pseudotyped virus have been developed, there have been few studies comparing the different assays to each other as surrogates for authentic virus neutralization. Here we characterized three enzyme-linked immunosorbent assays (ELISAs) and three pseudotyped VSV virus neutralization assays and assessed their concordance with authentic virus neutralization. The most accurate assays for predicting authentic virus neutralization were luciferase and secreted embryonic alkaline phosphatase (SEAP) expressing pseudotyped virus neutralizations, followed by GFP expressing pseudotyped virus neutralization, and then the ELISAs.

scholarly journals 564. SARS-CoV-2 Ferritin Nanoparticle Vaccines Elicit Broad SARS Coronavirus Immunogenicity

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S384-S384
Author(s):  
M G Joyce ◽  
Wei-Hung Chen ◽  
Rajeshwer Sankhala ◽  
Agnes Hajduczki ◽  
Paul Thomas ◽  
...  
Keyword(s):  
Immune Responses ◽  
Neutralizing Antibody ◽  
High Dose ◽  
Pandemic Preparedness ◽  
Virus Stock ◽  
Global Pandemic ◽  
Recent Emergence ◽  
Blocking Activity ◽  
Antibody Levels ◽  
Antigenic Profile

Abstract Background The zoonotic emergence of SARS-CoV-2 quickly developed into a global pandemic. Multiple vaccine platforms have been advanced to clinical trials and emergency use authorization. The recent emergence of SARS-CoV-2 virus variants with Spike receptor-binding domain (RBD) and N-terminal domain (NTD) mutations, highlights the need for next-generation vaccines that can elicit immune responses that are resilient against Spike mutations. Methods Using a structure-based vaccine design approach, we developed multiple optimized SARS-CoV-2 nanoparticle immunogens that recapitulate the structural and antigenic profile of the SARS-CoV-2 prefusion spike. We assessed these immunogens in murine immunogenicity studies and in a K18-hACE2 transgenic mouse model with a SARS-CoV-2 challenge. Immune sera from vaccinated mice were assessed for SARS-CoV-2 binding, and neutralization against SARS-CoV-2, variants of concern, and the heterologous SARS-CoV-1 virus. Results In combination with a liposomal-saponin based adjuvant (ALFQ), these immunogens induced robust binding, ACE2-inhibition, and authentic virus and pseudovirus neutralization. A Spike-Ferritin nanoparticle (SpFN) vaccine elicited neutralizing ID50 titers >10,000 after a single immunization, while RBD-Ferritin (RFN) nanoparticle immunogens elicited ID50 titer values >10,000 values after two immunizations. Purified antibody from SpFN- or RFN-immunized mice was transfused into K18-ACE2 transgenic mice and challenged with a high-dose SARS-CoV-2 virus stock. In order to understand the breadth of vaccine-elicited antibody responses, we analyzed SpFN- and RBD-FN-immunized animal sera against a set of heterologous SARS-CoV-2 RBD variants and SARS-CoV RBD. High binding titers with ACE2-blocking activity were observed against SARS-CoV-2 variants and the heterologous SARS-CoV-1 RBD. Furthermore, both SpFN- and RFN-immunized animal sera showed SARS-CoV-1 neutralizing ID50 titers of >2000. Conclusion These observations highlight the importance of SARS-CoV-2 neutralizing antibody levels in providing protection against emerging SARS-like coronaviruses and provide a robust platform for pandemic preparedness. Structure-based design enables development of a SARS-CoV-2 nanoparticle immunogen. Disclosures All Authors: No reported disclosures

scholarly journals Longitudinal dynamics of the neutralizing antibody response to SARS-CoV-2 infection

2020 ◽  
Author(s):  
Kai Wang ◽  
Quan-Xin Long ◽  
Hai-Jun Deng ◽  
Jie Hu ◽  
Qing-Zhu Gao ◽  
...  
Keyword(s):  
Proinflammatory Cytokines ◽  
Symptom Onset ◽  
Neutralizing Antibodies ◽  
Antiviral Agents ◽  
Neutralizing Antibody ◽  
Peak Time ◽  
Igg Antibody ◽  
Longitudinal Dynamics ◽  
Global Pandemic ◽  
Antibody Levels

Background Coronavirus disease 2019 (COVID-19) is a global pandemic with no licensed vaccine or specific antiviral agents for therapy. Little is known about the longitudinal dynamics of SARS-CoV-2-specific neutralizing antibodies (NAbs) in COVID-19 patients. Methods Blood samples (n=173) were collected from 30 COVID-19 patients over a 3-month period after symptom onset and analyzed for SARS-CoV-2-specific NAbs, using the lentiviral pseudotype assay, coincident with the levels of IgG and proinflammatory cytokines. Results SARS-CoV-2-specific NAb titers were low for the first 7-10 d after symtom onset and increased after 2-3 weeks. The median peak time for NAbs was 33 d (IQR 24-59 d) after symptom onset. NAb titers in 93.3% (28/30) of the patients declined gradually over the 3-month study period, with a median decrease of 34.8% (IQR 19.6-42.4%). NAb titers increased over time in parallel with the rise in IgG antibody levels, correlating well at week 3 (r = 0.41, p < 0.05). The NAb titers also demonstrated a significant positive correlation with levels of plasma proinflammatory cytokines, including SCF, TRAIL, and M-CSF. Conclusions These data provide useful information regarding dynamic changes in NAbs in COVID-19 patients during the acute and convalescent phases.

scholarly journals Variant SARS-CoV-2 mRNA vaccines confer broad neutralization as primary or booster series in mice

2021 ◽  
Author(s):  
Kai Wu ◽  
Angela Choi ◽  
Matthew Koch ◽  
Sayda Elbashir ◽  
LingZhi Ma ◽  
...  
Keyword(s):  
Phase 1 ◽  
Neutralizing Antibody ◽  
Primary Vaccination ◽  
Viral Escape ◽  
Phase 3 ◽  
S Protein ◽  
Global Pandemic ◽  
Primary Series ◽  
Antibody Titers ◽  
Induced Immunity

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of a global pandemic that has led to more than 2.8 million deaths worldwide. Safe and effective vaccines are now available, including Moderna's COVID-19 vaccine (mRNA-1273) that showed 94% efficacy in prevention of symptomatic COVID-19 disease in a phase 3 clinical study. mRNA-1273 encodes for a prefusion stabilized full length spike (S) protein of the Wuhan-Hu-1 isolate. However, the emergence of SARS-CoV-2 variants has led to concerns of viral escape from vaccine-induced immunity. Several emerging variants have shown decreased susceptibility to neutralization by vaccine induced immunity, most notably the B.1.351 variant, although the overall impact on vaccine efficacy remains to be determined. Here, we present the initial evaluation in mice of two updated COVID-19 mRNA vaccines designed to target emerging SARS-CoV-2 variants: (1) monovalent mRNA-1273.351 encodes for the S protein found in the B.1.351 lineage and (2) mRNA-1273.211 comprising a 1:1 mix of mRNA-1273 and mRNA-1273.351. Both vaccines were evaluated as a 2-dose primary series in mice; mRNA-1273.351 was also evaluated as a booster dose in animals previously vaccinated with 2-doses of mRNA-1273. The results demonstrated that a primary vaccination series of mRNA-1273.351 was effective at increasing neutralizing antibody titers against the B.1.351 lineage, while mRNA-1273.211 was most effective at providing broad cross-variant neutralization in mice. In addition, these results demonstrated a third dose of mRNA-1273.351 significantly increased both wild-type and B.1.351-specific neutralization titers. Both mRNA-1273.351 and mRNA-1273.211 are currently being evaluated in additional pre-clinical challenge models and in phase 1/2 clinical studies.

scholarly journals Transcutaneous Immunization with Cross-Reacting Material CRM197 of Diphtheria Toxin Boosts Functional Antibody Levels in Mice Primed Parenterally with Adsorbed Diphtheria Toxoid Vaccine

2008 ◽  
Vol 76 (4) ◽  
pp. 1766-1773 ◽  
Author(s):  
Paul Stickings ◽  
Marisa Peyre ◽  
Laura Coombes ◽  
Sylviane Muller ◽  
Rino Rappuoli ◽  
...  
Keyword(s):  
Immune Responses ◽  
Diphtheria Toxin ◽  
Neutralizing Antibodies ◽  
Time Course ◽  
Herd Immunity ◽  
Neutralizing Antibody ◽  
Diphtheria Toxoid ◽  
Booster Immunization ◽  
Transcutaneous Immunization ◽  
Antibody Levels

ABSTRACT Transcutaneous immunization (TCI) capitalizes on the accessibility and immunocompetence of the skin, elicits protective immunity, simplifies vaccine delivery, and may be particularly advantageous when frequent boosting is required. In this study we examined the potential of TCI to boost preexisting immune responses to diphtheria in mice. The cross-reacting material (CRM197) of diphtheria toxin was used as the boosting antigen and was administered alone or together with either one of two commonly used mucosal adjuvants, cholera toxin (CT) and a partially detoxified mutant of heat-labile enterotoxin of Escherichia coli (LTR72). We report that TCI with CRM197 significantly boosted preexisting immune responses elicited after parenteral priming with aluminum hydroxide-adsorbed diphtheria toxoid (DTxd) vaccine. In the presence of LTR72 as an adjuvant, toxin-neutralizing antibody titers were significantly higher than those elicited by CRM197 alone and were comparable to the functional antibody levels induced after parenteral booster immunization with the adsorbed DTxd vaccine. Time course study showed that high levels of toxin-neutralizing antibodies persisted for at least 14 weeks after the transcutaneous boost. In addition, TCI resulted in a vigorous antigen-specific proliferative response in all groups of mice boosted with the CRM197 protein. These findings highlight the promising prospect of using booster administrations of CRM197 via the transcutaneous route to establish good herd immunity against diphtheria.

scholarly journals Immunization with RBD-P2 and N protects against SARS-CoV-2 in nonhuman primates

2021 ◽  
Vol 7 (22) ◽  
pp. eabg7156
Author(s):  
So-Hee Hong ◽  
Hanseul Oh ◽  
Yong Wook Park ◽  
Hye Won Kwak ◽  
Eun Young Oh ◽  
...  
Keyword(s):  
Nucleocapsid Protein ◽  
Nonhuman Primates ◽  
Vaccine Candidate ◽  
Statistical Significance ◽  
Neutralizing Antibody ◽  
Spike Protein ◽  
Vaccine Candidates ◽  
Cell Responses ◽  
Antibody Levels ◽  
Further Development

Since the emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), various vaccines are being developed, with most vaccine candidates focusing on the viral spike protein. Here, we developed a previously unknown subunit vaccine comprising the receptor binding domain (RBD) of the spike protein fused with the tetanus toxoid epitope P2 (RBD-P2) and tested its efficacy in rodents and nonhuman primates (NHPs). We also investigated whether the SARS-CoV-2 nucleocapsid protein (N) could increase vaccine efficacy. Immunization with N and RBD-P2 (RBDP2/N) + alum increased T cell responses in mice and neutralizing antibody levels in rats compared with those obtained using RBD-P2 + alum. Furthermore, in NHPs, RBD-P2/N + alum induced slightly faster SARS-CoV-2 clearance than that induced by RBD-P2 + alum, albeit without statistical significance. Our study supports further development of RBD-P2 as a vaccine candidate against SARS-CoV-2. Also, it provides insights regarding the use of N in protein-based vaccines against SARS-CoV-2.

scholarly journals Association between season of vaccination and antibody levels against infectious diseases

2020 ◽  
Vol 148 ◽  
Author(s):  
T. C. Abreu ◽  
H. Boshuizen ◽  
L. Mollema ◽  
G. A. M. Berbers ◽  
H. Korthals Altes
Keyword(s):  
Disease Burden ◽  
Seasonal Cycles ◽  
Inclusion Criteria ◽  
Cross Sectional ◽  
Vaccine Preventable Diseases ◽  
Multivariable Regression ◽  
Immunological Protection ◽  
Antibody Levels ◽  
Induced Immunity ◽  
Tetanus Antibodies

Abstract Vaccination has reduced the disease burden of vaccine-preventable diseases. However, the extent to which seasonal cycles of immunity could influence vaccine-induced immunity is not well understood. A national cross-sectional serosurveillance study performed in the Netherlands (Pienter-2) yielded data to investigate whether season of vaccination was associated with antibody responses induced by DT-IPV (diphtheria, tetanus and poliomyelitis), MMR (measles, mumps and rubella) and meningococcus C (MenC) vaccines in children. In total, 434 children met the inclusion criteria to study DT-IPV immunity, 811 for MMR and 311 for MenC. Differences in log(antibody levels) by season of vaccination were investigated with linear multivariable regression analyses. Seroconversion rates varied according to season of vaccination for rubella (90% of autumn-vaccinated children vs. 99% of winter-vaccinated had concentrations above cut-off levels). Summer-vaccinated boys showed a slower decline of tetanus antibodies (6% per month), in comparison with winter-vaccinated boys. In conclusion, season of vaccination showed little association with immunological protection. However, a number of associations were seen with a P-value of about 0.03; and adding data from a just-completed nationwide serological study might add more power to the current study. Further immunological and longitudinal investigations could help understand the mechanisms of seasonal influence in vaccine-induced responses.

scholarly journals The Use of GIS Technology to Optimize COVID-19 Vaccine Distribution: A Case Study of the City of Warsaw, Poland

2021 ◽  
Vol 18 (11) ◽  
pp. 5636
Author(s):  
Sylwia Krzysztofowicz ◽  
Katarzyna Osińska-Skotak
Keyword(s):  
Herd Immunity ◽  
Research Work ◽  
Age Groups ◽  
Group Living ◽  
Population Group ◽  
Gis Technology ◽  
Vaccination Site ◽  
Global Challenge ◽  
Vaccine Distribution ◽  
The City

The COVID-19 pandemic is a global challenge, and the key to tackling it is vaccinating a specified percentage of the population to acquire herd immunity. The observed problems with the efficiency of the vaccination campaigns in numerous countries around the world, as well as the approach used at the initial stage of the National Immunization Program in Poland, prompted us to analyse the possibility of using GIS technology to optimize the distribution of vaccines to vaccination sites so as to minimize the period needed to vaccinate individual population groups. The research work was carried out on the example of Warsaw, the capital of Poland and the city with the largest population in the country. The analyses were carried out for the 60–70 and 50–60 age groups, in various approaches and for vaccines of different companies (Moderna, BioNTech, AstraZeneca), used to vaccinate people in Poland. The proposed approach to optimize vaccine distribution uses Thiessen’s tessellation to obtain information on the number of people in a given population group living in the area of each vaccination site, and then to estimate the time needed to vaccinate that group. Compared to the originally used vaccination scenario with limited availability of vaccines, the proposed approach allows practitioners to design fast and efficient distribution scenarios. With the developed methodology, we demonstrated ways to achieve uniform vaccination coverage throughout the city. We anticipate that the proposed approach can be easily automated and broadly applied to various urban settings.

scholarly journals Pneumococcal Nasopharyngeal Carriage following Reduced Doses of a 7-Valent Pneumococcal Conjugate Vaccine and a 23-Valent Pneumococcal Polysaccharide Vaccine Booster

2010 ◽  
Vol 17 (12) ◽  
pp. 1970-1976 ◽  
Author(s):  
F. M. Russell ◽  
J. R. Carapetis ◽  
C. Satzke ◽  
L. Tikoduadua ◽  
L. Waqatakirewa ◽  
...  
Keyword(s):  
Conjugate Vaccine ◽  
Pneumococcal Conjugate Vaccine ◽  
Polysaccharide Vaccine ◽  
Dose Effect ◽  
Pneumococcal Polysaccharide Vaccine ◽  
Pneumococcal Carriage ◽  
Primary Series ◽  
Vaccine Type ◽  
Vaccine Booster ◽  
Antibody Levels

ABSTRACT This study was conducted to evaluate the effect of a reduced-dose 7-valent pneumococcal conjugate vaccine (PCV) primary series followed by a 23-valent pneumococcal polysaccharide vaccine (23vPPS) booster on nasopharyngeal (NP) pneumococcal carriage. For this purpose, Fijian infants aged 6 weeks were randomized to receive 0, 1, 2, or 3 PCV doses. Within each group, half received 23vPPS at 12 months. NP swabs were taken at 6, 9, 12, and 17 months and were cultured for Streptococcus pneumoniae. Isolates were serotyped by multiplex PCR and a reverse line blot assay. There were no significant differences in PCV vaccine type (VT) carriage between the 3- and 2-dose groups at 12 months. NP VT carriage was significantly higher (P, <0.01) in the unvaccinated group than in the 3-dose group at the age of 9 months. There appeared to be a PCV dose effect in the cumulative proportion of infants carrying the VT, with less VT carriage occurring with more doses of PCV. Non-PCV serotype (NVT) carriage rates were similar for all PCV groups. When groups were pooled by receipt or nonreceipt of 23vPPS at 12 months, there were no differences in pneumococcal, VT, or NVT carriage rates between the 2 groups at the age of 17 months. In conclusion, there appeared to be a PCV dose effect on VT carriage, with less VT carriage occurring with more doses of PCV. By the age of 17 months, NVT carriage rates were similar for all groups. 23vPPS had no impact on carriage, despite the substantial boosts in antibody levels.

scholarly journals Antibody level of New Zealand children immunized with the triple vaccine DTP (diphtheria-tetanus-pertussis)

1988 ◽  
Vol 101 (2) ◽  
pp. 405-410 ◽  
Author(s):  
R. C. H Lau
Keyword(s):  
New Zealand ◽  
Immunosorbent Assay ◽  
Antibody Level ◽  
Herd Immunity ◽  
Enzyme Linked Immunosorbent Assay ◽  
Igg Antibody ◽  
Immunization Strategy ◽  
The Mean ◽  
Antibody Levels

SUMMARYEnzyme-linked immunosorbent assay (ELISA) tests were used to measure IgG antibody levels in 2638 New Zealand children who had been immunized with the triple vaccine DTP. The percentage of children immune to diphtheria decreased with age. The percentage of children immune to tetanus varied from 67.1 to 55.0%. The percentage of children with measurable antibody to pertussis increased with age. The mean percentages of children with measurable antibody or immunity to one or more DTP components were 34.2% (with 3 components), 34.4% (2 components), and 78.1% (1 component). It appears the immunization strategy for diphtheria and tetanus is satisfactory for herd immunity in New Zealand children. However, the current pertussis strategy may not be providing adequate immunity to 5-year-olds in this country.

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