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1.
NPJ Vaccines ; 7(1): 88, 2022 Aug 01.
Article in English | MEDLINE | ID: covidwho-1967607

ABSTRACT

mRNA vaccines can be developed and produced quickly, making them prime candidates for immediate outbreak responses. Furthermore, clinical trials have demonstrated rapid protection following mRNA vaccination. Thus, we sought to investigate how quickly mRNA vaccines elicit antibody responses compared to other vaccine modalities. We first compared the immune kinetics of mRNA and DNA vaccines expressing SARS-CoV-2 spike in mice. We observed rapid induction of antigen-specific binding and neutralizing antibodies by day 5 following mRNA (4 µg/mouse), but not DNA (50 µg/mouse), immunization. Comparing innate responses hours post immunization, the mRNA vaccine induced increased levels of IL-5, IL-6, and MCP-1 cytokines which maybe promoting humoral responses downstream. We then evaluated the immune kinetics of an HIV-1 mRNA vaccine in comparison to DNA, protein, and rhesus adenovirus 52 (RhAd52) vaccines of the same HIV-1 envelope antigen in mice. Again, induction of envelope-specific antibodies was observed by day 5 following mRNA vaccination, whereas antibodies were detected by day 7-14 following DNA, protein, and RhAd52 vaccination. Thus, eliciting rapid humoral immunity may be a unique and advantageous property of mRNA vaccines for controlling infectious disease outbreaks.

2.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-335701

ABSTRACT

Combining optimized spike (S) protein-encoding mRNA vaccines to target multiple SARS-CoV-2 variants could improve COVID-19 control. We compared monovalent and bivalent mRNA vaccines encoding B.1.351 (Beta) and/or B.1.617.2 (Delta) SARS-CoV-2 S-protein, primarily in a transgenic mouse model and a Wistar rat model. The low-dose bivalent mRNA vaccine contained half the mRNA of each respective monovalent vaccine, but induced comparable neutralizing antibody titres, enrichment of lung-resident memory CD8 + T cells, specific CD4 + and CD8 + responses, and fully protected transgenic mice from SARS-CoV-2 lethality. The bivalent mRNA vaccine significantly reduced viral replication in both Beta- and Delta-challenged mice. Sera from bivalent mRNA vaccine immunized Wistar rats also contained neutralizing antibodies against the B.1.1.529 (Omicron BA.1) variant. These data suggest that low-dose and fit-for-purpose multivalent mRNA vaccines encoding distinct S-proteins is a feasible approach for increasing the potency of vaccines against emerging and co-circulating SARS-CoV-2 variants.

3.
Paediatr Perinat Epidemiol ; 36(4): 476-484, 2022 07.
Article in English | MEDLINE | ID: covidwho-1794581

ABSTRACT

BACKGROUND: Multiple reports have described neonatal SARS-CoV-2 infection, including likely in utero transmission and early postnatal infection, but published estimates of neonatal infection range by geography and design type. OBJECTIVES: To describe maternal, pregnancy and neonatal characteristics among neonates born to people with SARS-CoV-2 infection during pregnancy by neonatal SARS-CoV-2 testing results. METHODS: Using aggregated data from the Surveillance for Emerging Threats to Mothers and Babies Network (SET-NET) describing infections from 20 January 2020 to 31 December 2020, we identified neonates who were (1) born to people who were SARS-CoV-2 positive by RT-PCR at any time during their pregnancy, and (2) tested for SARS-CoV-2 by RT-PCR during the birth hospitalisation. RESULTS: Among 28,771 neonates born to people with SARS-CoV-2 infection during pregnancy, 3816 (13%) underwent PCR testing and 138 neonates (3.6%) were PCR positive. Ninety-four per cent of neonates testing positive were born to people with infection identified ≤14 days of delivery. Neonatal SARS-CoV-2 infection was more frequent among neonates born preterm (5.7%) compared to term (3.4%). Neonates testing positive were born to both symptomatic and asymptomatic pregnant people. CONCLUSIONS: Jurisdictions reported SARS-CoV-2 RT-PCR results for only 13% of neonates known to be born to people with SARS-CoV-2 infection during pregnancy. These results provide evidence of neonatal infection identified through multi-state systematic surveillance data collection and describe characteristics of neonates with SARS-CoV-2 infection. While perinatal SARS-CoV-2 infection was uncommon among tested neonates born to people with SARS-CoV-2 infection during pregnancy, nearly all cases of tested neonatal infection occurred in pregnant people infected around the time of delivery and was more frequent among neonates born preterm. These findings support the recommendation for neonatal SARS-CoV-2 RT-PCR testing, especially for people with acute infection around the time of delivery.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19 Testing , Female , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/epidemiology , Pregnancy Outcome/epidemiology , SARS-CoV-2
4.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-331559

ABSTRACT

Objective: To describe prevalence of breastmilk feeding among people with SARS-CoV-2 infection during pregnancy and examine associations between breastmilk feeding, timing of maternal infection before delivery, and rooming-in status during delivery hospitalization. Methods Retrospective cohort using data from five states reporting initiation of breastmilk feeding of infants at birth among people with confirmed SARS-CoV-2 infection during pregnancy in 2020. Results Among 9760 (weighted N) people with SARS-CoV-2 infection in pregnancy, 86.0% (95% confidence interval [CI]: 83.3%-88.7%) initiated breastmilk feeding during birth hospitalization. People with infection ≤ 14 days before delivery had significantly lower prevalence of breastmilk feeding (adjusted prevalence ratio [aPR] 0.90, 95% CI: 0.82, 0.97) compared to those with infection > 14 days before delivery. When stratified by rooming-in status, the association between timing of infection and breastmilk feeding remained only among infants who did not room-in with their mother (aPR 0.78, 95% CI: 0.66, 0.92). Conclusion Pregnant and postpartum people with SARS-CoV-2 infection should be advised about the importance of breastmilk feeding, how to safely feed their infants in the same room, and have access to lactation support.

5.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-318348

ABSTRACT

Background: Multiple reports have described neonatal SARS-CoV-2 infection, including likely in utero transmission and early postnatal infection. Most neonatal infections reported to date have been asymptomatic or mild disease;however, severe cases, including respiratory failure requiring intensive care unit admission, have been described. Objectives: To describe maternal, pregnancy and infant characteristics among neonates born to women with SARS-CoV-2 infection during pregnancy by neonatal SARS-CoV-2 testing results. Methods: : Using aggregated data from the Surveillance for Emerging Threats to Mothers and Babies Network (SET-NET) from March 29, 2020–August 6, 2021, we identified neonates who were: 1) born to women who were SARS-CoV-2 positive by RT-PCR at any time during their pregnancy, and 2) tested for SARS-CoV-2 by RT-PCR during the birth hospitalization. Results: : Among 25,896 neonates of mothers with SARS-CoV-2-infection, 3,381 (13%) underwent PCR testing. One hundred thirty-six neonates (4%) were PCR-positive. Neonates testing positive were born to both symptomatic and asymptomatic women, and 95% were born to women with infection identified ≤ with 14 days of delivery. Conclusions: : While perinatal SARS-CoV-2 infection was uncommon among neonates born to women with SARS-CoV-2 infection during pregnancy, nearly all cases of neonatal infection occurred in pregnant women infected around the time of delivery. These findings underline the need for infection prevention and control measures in delivery and outpatient pediatric settings, as well as counselling for persons who acquire COVID-19 during pregnancy about potential risk to their neonates. Moreover, pregnant people and those wanting to become pregnant should be vaccinated against COVID-19 in order to protect themselves and their infants.

6.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324093

ABSTRACT

Introduction: Public health responses often lack the infrastructure to capture the impact of public health emergencies on pregnant women and infants, with limited mechanisms for linking pregnant women with their infants nationally to monitor long-term effects. In 2019, the Centers for Disease Control and Prevention (CDC), in close collaboration with state, local, and territorial health departments, began a five-year initiative to establish population-based mother-baby linked longitudinal surveillance, the Surveillance for Emerging Threats to Mothers and Babies Network (SET-NET). Objectives: The objective of this report is to describe an expanded surveillance approach that leverages and modernizes existing surveillance systems to address the impact of emerging health threats during pregnancy on pregnant women and their infants. Methods: Mother-baby pairs are identified prospectively during pregnancy and/or retrospectively after birth of the infant. All data are obtained from existing data sources (e.g., electronic medical records, vital statistics, laboratory reports, and health department investigations and case reporting). Results: Variables were selected for inclusion to address key surveillance questions proposed by CDC and health department subject matter experts. General variables include maternal demographics and health history, pregnancy and infant outcomes, maternal and infant laboratory results, and child health outcomes up to the second birthday. Exposure-specific modular variables are included for hepatitis C, syphilis, and Coronavirus Disease 2019 (COVID-19). The system is structured into four relational datasets (maternal, pregnancy outcomes and birth, infant/child follow-up, and laboratory testing). Discussion: SET-NET provides a population-based mother-baby linked longitudinal surveillance approach and has demonstrated rapid adaptation for use during COVID-19. This innovative approach leverages existing data sources and rapidly collects data to inform clinical guidance and practice. These data can help to reduce exposure risk and adverse outcomes among pregnant women and their infants, direct public health action, and strengthen public health systems.

7.
Nature ; 601(7893): 410-414, 2022 01.
Article in English | MEDLINE | ID: covidwho-1521758

ABSTRACT

The CVnCoV (CureVac) mRNA vaccine for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was recently evaluated in a phase 2b/3 efficacy trial in humans1. CV2CoV is a second-generation mRNA vaccine containing non-modified nucleosides but with optimized non-coding regions and enhanced antigen expression. Here we report the results of a head-to-head comparison of the immunogenicity and protective efficacy of CVnCoV and CV2CoV in non-human primates. We immunized 18 cynomolgus macaques with two doses of 12 µg lipid nanoparticle-formulated CVnCoV or CV2CoV or with sham (n = 6 per group). Compared with CVnCoV, CV2CoV induced substantially higher titres of binding and neutralizing antibodies, memory B cell responses and T cell responses as well as more potent neutralizing antibody responses against SARS-CoV-2 variants, including the Delta variant. Moreover, CV2CoV was found to be comparably immunogenic to the BNT162b2 (Pfizer) vaccine in macaques. Although CVnCoV provided partial protection against SARS-CoV-2 challenge, CV2CoV afforded more robust protection with markedly lower viral loads in the upper and lower respiratory tracts. Binding and neutralizing antibody titres were correlated with protective efficacy. These data demonstrate that optimization of non-coding regions can greatly improve the immunogenicity and protective efficacy of a non-modified mRNA SARS-CoV-2 vaccine in non-human primates.


Subject(s)
COVID-19 Vaccines/genetics , COVID-19 Vaccines/immunology , COVID-19/prevention & control , Immunogenicity, Vaccine , Nucleosides/chemistry , Vaccines, Synthetic/genetics , Vaccines, Synthetic/immunology , /immunology , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , COVID-19/virology , COVID-19 Vaccines/standards , Female , Macaca fascicularis/immunology , Male , Nucleosides/genetics , Respiratory System/immunology , Respiratory System/virology , SARS-CoV-2/immunology , T-Lymphocytes/immunology , Vaccines, Synthetic/standards , Viral Load , /standards
8.
Nat Commun ; 12(1): 4048, 2021 06 30.
Article in English | MEDLINE | ID: covidwho-1290662

ABSTRACT

The ongoing SARS-CoV-2 pandemic necessitates the fast development of vaccines. Recently, viral mutants termed variants of concern (VOC) which may escape host immunity have emerged. The efficacy of spike encoding mRNA vaccines (CVnCoV and CV2CoV) against the ancestral strain and the VOC B.1.351 was tested in a K18-hACE2 transgenic mouse model. Naive mice and mice immunized with a formalin-inactivated SARS-CoV-2 preparation were used as controls. mRNA-immunized mice develop elevated SARS-CoV-2 RBD-specific antibody and neutralization titers which are readily detectable, but significantly reduced against VOC B.1.351. The mRNA vaccines fully protect from disease and mortality caused by either viral strain. SARS-CoV-2 remains undetected in swabs, lung, or brain in these groups. Despite lower neutralizing antibody titers compared to the ancestral strain BavPat1, CVnCoV and CV2CoV show complete disease protection against the novel VOC B.1.351 in our studies.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19 Vaccines/immunology , COVID-19/prevention & control , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/immunology , Animals , Cell Line , Chlorocebus aethiops , Genome, Viral/genetics , Humans , Mice , Mice, Transgenic , SARS-CoV-2/genetics , Vero Cells
9.
NPJ Vaccines ; 6(1): 57, 2021 Apr 16.
Article in English | MEDLINE | ID: covidwho-1189227

ABSTRACT

mRNA technologies have recently proven clinical efficacy against coronavirus disease 2019 and are among the most promising technologies to address the current pandemic. Here, we show preclinical data for our clinical candidate CVnCoV, a lipid nanoparticle-encapsulated mRNA vaccine that encodes full-length, pre-fusion stabilised severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein. In contrast to previously published approaches, CVnCoV is exclusively composed of naturally occurring nucleotides. Immunisation with CVnCoV induced strong humoral responses with high titres of virus-neutralising antibodies and robust T-cell responses. CVnCoV vaccination protected hamsters from challenge with wild-type SARS-CoV-2, demonstrated by the absence of viral replication in the lungs. Hamsters vaccinated with a suboptimal dose of CVnCoV leading to breakthrough viral replication exhibited no evidence of vaccine-enhanced disease. Overall, data presented here provide evidence that CVnCoV represents a potent and safe vaccine candidate against SARS-CoV-2.

10.
Matern Child Health J ; 25(2): 198-206, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-1006455

ABSTRACT

INTRODUCTION: Public health responses often lack the infrastructure to capture the impact of public health emergencies on pregnant women and infants, with limited mechanisms for linking pregnant women with their infants nationally to monitor long-term effects. In 2019, the Centers for Disease Control and Prevention (CDC), in close collaboration with state, local, and territorial health departments, began a 5-year initiative to establish population-based mother-baby linked longitudinal surveillance, the Surveillance for Emerging Threats to Mothers and Babies Network (SET-NET). OBJECTIVES: The objective of this report is to describe an expanded surveillance approach that leverages and modernizes existing surveillance systems to address the impact of emerging health threats during pregnancy on pregnant women and their infants. METHODS: Mother-baby pairs are identified through prospective identification during pregnancy and/or identification of an infant with retrospective linking to maternal information. All data are obtained from existing data sources (e.g., electronic medical records, vital statistics, laboratory reports, and health department investigations and case reporting). RESULTS: Variables were selected for inclusion to address key surveillance questions proposed by CDC and health department subject matter experts. General variables include maternal demographics and health history, pregnancy and infant outcomes, maternal and infant laboratory results, and child health outcomes up to the second birthday. Exposure-specific modular variables are included for hepatitis C, syphilis, and Coronavirus Disease 2019 (COVID-19). The system is structured into four relational datasets (maternal, pregnancy outcomes and birth, infant/child follow-up, and laboratory testing). DISCUSSION: SET-NET provides a population-based mother-baby linked longitudinal surveillance approach and has already demonstrated rapid adaptation to COVID-19. This innovative approach leverages existing data sources and rapidly collects data and informs clinical guidance and practice. These data can help to reduce exposure risk and adverse outcomes among pregnant women and their infants, direct public health action, and strengthen public health systems.


Subject(s)
Civil Defense/methods , Mother-Child Relations , Population Surveillance/methods , Adult , COVID-19/complications , COVID-19/diagnosis , Civil Defense/instrumentation , Female , Hepatitis C/complications , Hepatitis C/diagnosis , Humans , Infant, Newborn , Mass Screening/methods , Pregnancy , Syphilis/complications , Syphilis/diagnosis
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