Analysis of the immune response using FTIR spectroscopy in mothers and their newborns with different vaccination schemes for COVID-19 – Nature.com

As previously mentioned, we analyzed the bands associated with the humoral and cellular immunological responses generated on newborns by vaccinated mothers, establishing a relationship between the immunity induced in mothers and their children.

According to the data obtained in this research, the VV vaccine was the most frequently used in mothers' immunization against SARS-CoV-2. The Ministry of Health of the government of Mexico declared that 150 million 345 thousand 255 vaccines against COVID-19 were applied in the country from December 24, 2020, to October 24, 2022, corresponding 54.78 million doses (36.44%) to the AstraZeneca brand (VV vaccine), being the most applied vaccine against COVID-19 in Mexico19, which is concordant with the data obtained herein.

On the other hand, the height and weight of the infants were as expected, like those data reported by other studies on Mexican people20.

Moreover, as mentioned in the results section, some differences between the saliva samples of the mothers and their children were observed. It is essential to note that most of the knowledge of salivary composition has been driven in adults, and very little is known about saliva in newborns. However, Hyyppa et al., among other authors, declared that salivary total protein content is significantly higher among adults than in children21. And it has been reported that neonatal salivary amylase concentrations are moderately low but rise to adult levels by one year22,23,24, which is concordant with the spectra obtained herein where the absorption bands related to proteins (amide I and amide II) are under-expressed in saliva newborns compared to the mothers.

On the other hand, the band associated with carbohydrates showed shifts, indicating the hydrolysis and metabolism during fermentation25. Gothefors et al. stated that the saliva of newborns has a very high lactoperoxidase activity, and it is known that pancreatic amylase does not contribute substantially to starch or glucose polymer digestion in newborns. Salivary amylase and mucosal -glucosidases appear adequate for glucose polymer digestion26.

Concerning the analysis of the humoral immune response, maternal immunization is a critical way to protect infants younger than six months of age from COVID-19. The vaccine produces SARS-CoV-2 specific antibodies in maternal circulation, which are transferred across the placenta barrier. It is well known that IgG is the only isotype actively transported from mother to child. However, several studies have demonstrated the presence of IgA in umbilical cord blood and fetal tissues, suggesting that the IgA detected in neonatal blood is exclusively of fetal origin27. Nevertheless, the effect of maternal COVID19 vaccines before pregnancy on infants has not been deeply studied. Yang et al. declared that maternal SARS-CoV-2 IgG antibodies produced from inactivated COVID-19 vaccine before pregnancy can be transferred to newborns by the placenta, which has been helpful for infants28. In this regard, it was observed that the mothers that received the VV and mRNA vaccines BP could generate a greater content of IgG and IgA in their children, noticing that this content decreased according to the time of vaccination during pregnancy (Fig.3). Nonetheless, the analysis of the integrated areas did not show statistical significance for IgG and IgA in the VV vaccine. However, the mRNA vaccines showed statistical significance in the immunoglobins and cytokine analyzed (Fig.4).

In the same way, the spectra of the saliva samples of the mothers evidenced that the band attributed to IgG showed that for VV and mRNA vaccines, the BP subgroup depicted a higher absorbance compared to the subgroups that received the vaccine during pregnancy (Fig.6), showing statistical significance only the mRNA vaccine in the analysis of the integrated areas (Fig.7). The above is probably because, during pregnancy, significant adaptations occur in the maternal immune system to avoid detrimental immune responses against the fetus. Moreover, some authors have reported reduced circulating B in the third trimester because of the elevated estrogens on lymphopoiesis. However, some studies suggest that total IgG levels remain stable during pregnancy, while others show a decrease in late pregnancy. In the same way, some evidence, mainly from the 1960s-1970s, supports no significant change in IgA levels during pregnancy; other data suggest more dynamic changes to occur during pregnancy29.

Moreover, some authors have stated that human infants receive most maternal immunoglobulins, predominantly IgG, via the placenta. IgG antibodies are usually passively transferred across the placenta from mother to fetus from the second trimester of pregnancy30. The IgG levels in the fetal circulation are relatively low (510% of maternal levels) between weeks 17 and 22, reaching 50% of maternal levels by week 32)31. Herein, we demonstrated that passive immunity is also activated from the first trimester of pregnancy, showing even a more significant amount of IgG in the mother's vaccinated newborns employing the mRNA vaccine (Fig.4).

It has been reported that the pathogenesis of COVID-19 involves both humoral and cellular immunological responses, and it is supposed that COVID-19 vaccines also elicited effective cell immune response, specifically IFN-, which is secreted by SARS-CoV-2-specific T-helper 1 and T-cytotoxic cells, reason by which in this research we also decided to analyze IFN-32.

The results of the band related to IFN- in the BP subgroup in newborns depicted a lower absorbance in the VV vaccine compared to the groups that received the vaccination during pregnancy. On the contrary, in the mRNA group, the higher absorbance was observed in the BP subgroup, decreasing after that in the subgroups that received the vaccination during pregnancy (Fig.3), showing statistical significance (Fig.4).

It has been reported that the numbers of T cells during pregnancy are lower than before pregnancy and that the percentage of IFN--producing CD4+cells is lower in the third trimester29, concordant with the results observed in the mRNA group.

For all those mentioned above, we can state that both vaccines (mRNA and VV) generated a more significant immune response in the newborns and their mothers when they applied BP compared to the vaccines used during pregnancy, showing statistical significance with the mRNA vaccine. However, when comparing the vaccine's humoral immune response BP, we observed no differences in the newborn's response, but their mother's mRNA vaccine generated a more significant humoral immune response. It has been reported that mRNA vaccines in a homologous regimen induce strong antibody responses to SARS-CoV-2 compared to other vaccine platforms. In contrast, viral vector and inactivated vaccines show satisfactory immunogenicity in a heterologous regimen, especially in combination with mRNA vaccines33. However, it is essential to mention that the patients included in this study only received one dose in the last year. Moreover, Rijkers reported that mRNA vaccines induced a potent humoral response. Upon influenza mRNA vaccination of non-human primates, germinal centers were observed in the draining lymph nodes, and antigen-specific follicular helper T cells were detected, being an ideal niche conducive to B cell activation, antibody isotype switching, and affinity maturation, leading to long-lived memory B cells and plasma cells34.

Analyzing all these results, we can state that the VV vaccine generated a greater humoral and cellular immune response than the mRNA vaccine in the mothers when it was applied in the STP; in the same way, the newborns of these mothers evidenced more significant amounts of IgA and IFN-. On the contrary, in the mothers, the mRNA vaccines showed a greater humoral immune response (IgG and IgA) when the vaccine was applied BP, compared to the VV vaccine, evidencing statistical significance (Fig.8).

About the cellular and humoral immune response correlation between newborns and their mothers, it was observed that the two vaccines (VV and mRNA) exhibited a positive correlation regarding IgG when the vaccine was administrated BP, which has been previously explained by the IgG passively transferred across the placenta from mother to fetus30,35. Moreover, Palmeira et al. reported that IgG is the only antibody class that significantly crosses the human placenta, which might depend on different factors, one of them the maternal levels of total IgG and specific antibodies, being the total IgG concentrations in cord sera lower than in their mothers36, which was also seen in this research.

It is essential to mention that BP in the VV group, a positive correlation was observed between newborns and mothers in IgG, IgA, and IFN-; the above might be explained once VV vaccines induce both innate and adaptive immune responses, recapitulating the natural infection process of specific pathogens, triggering classical acute inflammation and immune detection through the natural production of PAMPs37.

In the same way, a strong positive correlation was observed between newborns and their mothers on IgG and IgA when the mRNA vaccine was administrated at the STP. About this, Konje et al. have stated that the transplacental transfer of antibodies starts in the second trimester38. Similarly, Kugelman et al. declared that mRNA vaccination in the third trimester was associated with a strong maternal humoral IgG response that crossed the placenta and approached maternal titers in the newborn39, which might explain the results obtained herein.

Fouda et al. reported that maternal IgG can be detected in cord blood as early as 810weeks of gestation. However, only small amounts of maternal IgG are transferred in the first trimester ( 10%), reaching 50% of the maternal IgG in infant cord blood by the 30weeks of gestation, possibly due to an increase in the surface area of IgG uptake from maternal blood with higher gestational age40.

So, despite the VV vaccine being evidenced to produce a significant humoral and cellular immune response in newborns and their mothers when they received the vaccine at the STP, compared with the mRNA vaccine, no correlation was observed between newborns and their mothers. However, a moderate positive correlation was observed when BP applied this vaccine.

Moreover, even though the mRNA vaccine showed a more significant humoral immunity generation in newborns and their mothers when it was administrated BP, compared with the VV vaccine, it only showed statistical significance in the mothers. However, IgG showed a moderate positive correlation between the newborns and their mothers.

Finally, as mentioned before, in the correlation between cellular and humoral response on newborns and their mothers, only the mRNA vaccine group evidenced a strong correlation in mothers between IFN- and IgG when it was applied at the FTP, noticing no correlation or moderate correlation at the others moments of application or with the VV vaccine (Table 5). Some authors have indicated a difference between humoral and cellular responses41. Moreover, some authors, such as Menges et al., reported heterogeneity of antibody and T cell immune responses after SARS-CoV-2 infection. Indicating that the relationship between antibody and T-cell responses showed a weak to moderate positive correlation early after infection, which decreased over time42.

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Analysis of the immune response using FTIR spectroscopy in mothers and their newborns with different vaccination schemes for COVID-19 - Nature.com