Multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that have mutations associated with increased transmission and antibody escape have arisen over the course of the current pandemic. Although the current vaccines have largely been effective against past variants, the number of mutations found on the Omicron (B.1.1.529) spike protein appear to diminish the protection conferred by preexisting immunity. Using vesicular stomatitis virus (VSV) pseudoparticles expressing the spike protein of several SARS-CoV-2 variants, we evaluated the magnitude and breadth of the neutralizing antibody response over time in individuals after infection and in mRNA-vaccinated individuals. We observed that boosting increases the magnitude of the antibody response to wild-type (D614), Beta, Delta, and Omicron variants; however, the Omicron variant was the most resistant to neutralization. We further observed that vaccinated healthy adults had robust and broad antibody responses, whereas responses may have been reduced in vaccinated pregnant women, underscoring the importance of learning how to maximize mRNA vaccine responses in pregnant populations. Findings from this study show substantial heterogeneity in the magnitude and breadth of responses after infection and mRNA vaccination and may support the addition of more conserved viral antigens to existing SARS-CoV-2 vaccines. Description Preexisting neutralizing antibody activity is diminished against SARS-CoV-2 Omicron spike-expressing pseudoparticles relative to the D164 spike. Antibodies versus variants Understanding how antibodies elicited by SARS-CoV-2 infection or vaccination respond to variants of concern is essential, particularly as the Omicron variant becomes dominant globally. Here, Sievers et al. tested the capacity of serum or plasma from individuals infected with or vaccinated against SARS-CoV-2 to neutralize pseudoviruses expressing spike proteins from wild-type (D614) SARS-CoV-2 or from the Beta, Delta, and Omicron variants of concern. To do so, they studied three cohorts: individuals infected with SARS-CoV-2, pregnant individuals who received two doses of mRNA vaccine, and health care workers who received two doses of mRNA vaccine plus a booster dose. The authors consistently found poorer neutralization of Beta and Omicron spike protein–expressing pseudoviruses, though boosting improved neutralization activity. These findings support the administration of booster vaccines and add to our understanding the degree to which the Omicron variant evades immune responses.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8891085

Antibodies elicited by SARS-CoV-2 infection or mRNA vaccines have reduced neutralizing activity against Beta and Omicron pseudoviruses

Messenger RNA (mRNA) vaccines against COVID‐19 are the first authorized biological preparations developed using this platform. During the pandemic, their administration has been proven to be a life‐saving intervention. Here, we review the main advantages of using mRNA vaccines, identify further technological challenges to be met during the development of the mRNA platform, and provide an update on the clinical progress on leading mRNA vaccine candidates against different viruses that include influenza viruses, human immunodeficiency virus 1, respiratory syncytial virus, Nipah virus, Zika virus, human cytomegalovirus, and Epstein‐Barr virus. The prospects and challenges of manufacturing mRNA vaccines in low‐income countries are also discussed. The ongoing interest and research in mRNA technology are likely to overcome some existing challenges for this technology (e.g., related to storage conditions and immunogenicity of some components of lipid nanoparticles) and enhance the portfolio of vaccines against diseases for which classical formulations are already authorized. It may also open novel pathways of protection against infections and their consequences for which no safe and efficient immunization methods are currently available.

mRNA vaccines: The future of prevention of viral infections?

Explosive developments in mRNA vaccine technology in the last decade have made it possible to achieve great success in clinical trials of mRNA vaccines to prevent infectious diseases and develop cancer treatments and mRNA-based gene therapy products. The approval of the mRNA-1273 and BNT162b2 mRNA vaccines against SARS-CoV-2 by the U.S. Food and Drug Administration has led to mass vaccination (with mRNA vaccines) of several hundred million people around the world, including children. Despite its effectiveness in the fight against COVID-19, rare adverse effects of the vaccination have been shown in some studies, including vascular microcirculation disorders and autoimmune and allergic reactions. The biodistribution of mRNA vaccines remains one of the most poorly investigated topics. This mini-review discussed the results of recent experimental studies on humans and rodents regarding the biodistribution of mRNA vaccines, their constituents (mRNA and lipid nanoparticles), and their encoded antigens. We focused on the dynamics of the biodistribution of mRNA vaccine products and on the possibility of crossing the blood–brain and blood–placental barriers as well as transmission to infants through breast milk. In addition, we critically assessed the strengths and weaknesses of the detection methods that have been applied in these articles, whose results’ reliability is becoming a subject of debate.

Biodistribution of RNA Vaccines and of Their Products: Evidence from Human and Animal Studies

Coronavirus disease 2019 (COVID-19) is a respiratory disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). It is acknowledged that vulnerable people can suffer from mortal complications of COVID-19. Therefore, strengthening the immune system particularly in the most fragile people could help to protect them from infection. First, general nutritional status and food consumption patterns of everyone affect the effectiveness of each immune system. The effects of nutrition could impact the level of intestinal and genital microbiota, the adaptive immune system, and the innate immune system. Indeed, immune system cells and mediators, which are crucial to inflammatory reaction, are in the structures of fats, carbohydrates, and proteins and are activated through vitamins (vit) and minerals. Therefore, the association of malnutrition and infection could damage the immune response, reducing the immune cells and amplifying inflammatory mediators. Both amount and type of dietary fat impact on cytokine biology, that consequently assumes a crucial role in inflammatory disease. This review explores the power of nutrition in the immune response against COVID-19 infection, since a specific diet could modify the cytokine storm during the infection phase. This can be of vital importance in the most vulnerable subjects such as pregnant women or cancer patients to whom we have deemed it necessary to dedicate personalized indications.

/pdf/nutrition-as-personalized-medicine-against-sars-cov-2-3104iua2.pdf

Nutrition as Personalized Medicine against SARS-CoV-2 Infections: Clinical and Oncological Options with a Specific Female Groups Overview

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9941309

Safety and Effectiveness of Maternal COVID-19 Vaccines Among Pregnant People and Infants

Abstract Studies are needed to evaluate the safety and effectiveness of mRNA SARS-CoV-2 vaccination during pregnancy, and the levels of protection provided to their newborns through placental transfer of antibodies. Here, we evaluate the transplacental transfer of mRNA vaccine products and functional anti-SARS-CoV-2 antibodies during pregnancy and early infancy in a cohort of 20 individuals vaccinated during late pregnancy. We find no evidence of mRNA vaccine products in maternal blood, placenta tissue, or cord blood at delivery. However, we find time-dependent efficient transfer of IgG and neutralizing antibodies to the neonate that persists during early infancy. Additionally, using phage immunoprecipitation sequencing, we find a vaccine-specific signature of SARS-CoV-2 Spike protein epitope binding that is transplacentally transferred during pregnancy. Timing of vaccination during pregnancy is critical to ensure transplacental transfer of protective antibodies during early infancy. 

/pdf/evaluation-of-transplacental-transfer-of-mrna-vaccine-2icbwarn.pdf

Evaluation of transplacental transfer of mRNA vaccine products and functional antibodies during pregnancy and infancy

Key Points Question What is the association between reactogenicity and immunogenicity of mRNA COVID-19 vaccines in pregnancy? Findings In this cohort study of 76 individuals who received messenger RNA (mRNA) COVID-19 vaccines in pregnancy, systemic symptoms after vaccination were associated with 90% higher IgG titers after the second dose, and symptoms were associated with 6.3-fold higher cord blood IgG titers than in individuals without symptoms; there were no adverse outcomes. Offspring had positive IgG titers for at least 5 to 6 months of life. Meaning These results suggest that mRNA COVID-19 vaccines in pregnancy provoke an IgG response for the mother-infant dyad for 6 months after birth, and that systemic symptoms after vaccination may indicate a more robust immune response, without adverse outcomes.

Assessment of Adverse Reactions, Antibody Patterns, and 12-month Outcomes in the Mother-Infant Dyad After COVID-19 mRNA Vaccination in Pregnancy

Despite universal recommendations for COVID-19 mRNA vaccination in pregnancy, uptake has been lower than desired. There have been limited studies of the direct impact of COVID-19 mRNA vaccine exposure in human placental tissue. Using a primary human placental explants model, we investigated the uptake of two common mRNA vaccines (BNT162b2 Pfizer-BioNTech or mRNA-1273 Moderna), and whether exposure altered villous cytokine responses. Explants derived from second or third trimester chorionic villi were incubated with vaccines at supraphysiologic concentrations and analyzed at two time points. We observed minimal uptake of mRNA vaccines in placental explants by in situ hybridization and quantitative RT-PCR. No specific or global cytokine response was elicited by either of the mRNA vaccines in multiplexed immunoassays. Our results suggest that the human placenta does not readily absorb the COVID-19 mRNA vaccines nor generate a significant inflammatory response after exposure. 

Minimal mRNA uptake and inflammatory response to COVID-19 mRNA vaccine exposure in human placental explants.

Despite universal recommendations for COVID-19 mRNA vaccination in pregnancy, uptake has been lower than desired. There have been limited studies of the direct impact of COVID-19 mRNA vaccine exposure in human placental tissue. Using a primary human villous explant model, we investigated the uptake of two common mRNA vaccines (BNT162b2 Pfizer-BioNTech or mRNA-1273 Moderna), and whether exposure altered villous cytokine responses. Explants derived from second or third trimester chorionic villi were incubated with vaccines at supraphysiologic concentrations and analyzed at two time points. We observed minimal uptake of mRNA vaccines in placental explants by in situ hybridization and quantitative RT-PCR. No specific or global cytokine response was elicited by either of the mRNA vaccines in multiplexed immunoassays. Our results suggest that the human placenta does not readily absorb the COVID-19 mRNA vaccines nor generate a significant inflammatory response after exposure.

/pdf/minimal-mrna-uptake-and-inflammatory-response-to-covid-19-2lb9mi1r.pdf

Minimal mRNA uptake and inflammatory response to COVID-19 mRNA vaccine exposure in human placental explants

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Evaluation of transplacental transfer of mRNA vaccine products and functional antibodies during pregnancy and infancy

Assessment of Adverse Reactions, Antibody Patterns, and 12-month Outcomes in the Mother-Infant Dyad After COVID-19 mRNA Vaccination in Pregnancy

Minimal mRNA uptake and inflammatory response to COVID-19 mRNA vaccine exposure in human placental explants.

Minimal mRNA uptake and inflammatory response to COVID-19 mRNA vaccine exposure in human placental explants