Friday , September 24 2021

SARS-CoV-2 spike-specific antibodies induced in breast milk by COVID-19 vaccines

With the onset of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), scientists have started an intense work to develop a vaccine against the virus. These efforts were largely bolstered by predictions that public health interventions would inevitably cripple the global economy if continued indefinitely.

The first vaccine to receive emergency use authorization in the United States was the Pfizer/BioNTech messenger ribonucleic acid (mRNA) vaccine, and the Moderna mRNA vaccine was approved soon after. By February 26, 2021, the Johnson & Johnson (J&J)/Janssen human adenovirus (Ad26) vaccine has also been approved in the United States. As of July 27, 2021, 188 million people in the United States had received at least one dose, of which 191 and 138 million doses were provided by Pfizer and Moderna, respectively.

Study: Comparative profiles of milk antibodies specific to SARS-CoV-2 Spike elicited by COVID-19 vaccines currently authorized in the US. Image Credit: Ahmet Mısırlıgül /

COVID-19 in children

An interesting new article examines how these vaccines can help young patient populations survive the virus. Natural infection or vaccination of the mother causes the secretion of SARS-CoV-2 antibodies into breast milk, providing passive immunity to the baby.

Although young children and infants in many countries are not eligible for the COVID-19 vaccine, approximately 10% of patients in this age group infected with SARS-CoV-2 will experience symptoms severe enough to require intensive care. Although rare, some young COVID-19 patients may develop a potentially fatal sequel called Multisystem Inflammatory Syndrome in Children (MIS-C).

Adding to the risk of MIS-C, some children recovering from COVID-19 have reported prolonged symptoms even after the infection has resolved. In addition to the risks that patients bring to themselves, this group can transmit the virus to others while asymptomatic.

Taken together, these factors support the need to vaccinate both young children and infants against COVID-.19.

antibodies in milk

Human breast milk contains a total concentration of immunoglobulin (Ig) of about 0.6 mg/mL, mostly in the form of IgA (90%). IgA in breast milk is almost always secretory IgA, with secretory IgM accounting for about 8%.

The remaining 2% of breast milk Ig is mainly IgG originating from serum. Both secretory IgA and IgM are derived from gut-associated lymphoid tissue (GALT), some from B cells in mucosa-associated lymphoid tissue (MALT).

Natural infection with SARS-CoV-2 results in predominantly secretory IgA in breast milk. By comparison, 14 days after the second dose, breast milk appears primarily rich in IgG. Although the first dose of vaccine typically elicits an IgA dominant response in milk, the second dose fails to produce this type of antibody.

How was the work carried out?

The current study, a follow-up to a previous article, compares antibody composition in breast milk following vaccination with any of three vaccines currently available in the United States. The study was performed on samples collected from 50 different nursing mothers with mRNA and J&J vaccines one week before and 14 or 28 days after the second vaccine dose, respectively.

None of the subjects had a history of SARS-CoV-2 infection, and any milk samples prior to vaccination did not contain SARS-CoV-2-specific IgA.

What were the findings?

The findings show that mean specific milk IgG levels were similar between mRNA vaccines but higher than those achieved with the J&J vaccine.

Upon receipt of the mRNA vaccines, all samples were found to contain IgG antibodies specific to the SARS-CoV-2 spike protein. With the J&J vaccine, this probability was about 40% less. IgG titers in samples specific for spike-specific antibodies were also significantly reduced compared to breast milk samples from Moderna vaccine recipients.

Milk antibody response specific to SARS-CoV-2 Spike caused by COVID-19 vaccine. Plates were coated with full-length recombinant trimeric SARS-CoV-2 Spike. The milk was titrated and added to the dish. Plates were washed and blocked and incubated with the appropriate secondary antibody. Titration curves were plotted and used to calculate endpoint titers. (A) IgG titration curves (upper panel) and endpoint titers (lower panel). (B) IgA titration curves (upper panel) and endpoint titers (lower panel). (C) Secretory antibody titration curves (upper panel) and endpoint titers (lower panel). Dotted lines indicate positive cutoff values. Responders (%): Percentage of participants receiving this type of vaccine who exhibited positive endpoint titers. ****p<0.0001; *0.009

Approximately 70% and 50% of samples from Moderna and Pfizer vaccine recipients, respectively, had spiked IgA in milk without much difference in titer values. In addition, the Moderna vaccine produced a 93% higher increase in secretory IgA, which was approximately 74% and 54% comparable to the Pfizer and J&J vaccines, respectively. Overall, the level of vaccine-induced secretory antibodies was low in all vaccines, whether measured in absolute terms or compared with post-infection titers.

Among the three vaccines, about a quarter of Moderna vaccine recipients had higher titer than the other two vaccines. 86% of Moderna recipients showed an increase in antibody titers, while Pfizer and J&J recipients showed a smaller increase of 61%.

Relative increases in milk antibody reactivity to SARS-CoV-2 Spike elicited by COVID-19 vaccination. The endpoint titers were determined as follows: one for milk samples from participants 1 week before and within 14 (Pfizer/Moderna) or 28 (J&J) days of completion of a vaccination regimen. Pre-vaccine and post-vaccine endpoint titers are shown for: (A) IgG reactivity. (B) IgA reactivity. (C) Secretory antibody reactivity. Left panel, Moderna vaccine; middle panel, Pfizer vaccine; right panel, J&J vaccine. Each graph shows the percentage of vaccine recipients with >2-fold increase in specific endpoint titer among pre- and post-vaccine milk samples. (D) Fold increases in endpoint titers are shown for each vaccine group as indicated. ****p<0.0001; **0.0001

What are the effects?

NS The J&J vaccine weakly elicits spike-specific Ab in milk compared to mRNA-based vaccines and should be considered as a last resort option for immunization for those wishing to elicit a strong Ab response in their milk.

Breastmilk antibody response can be moderately enhanced by the Moderna vaccine in terms of secretory IgA titers compared to other vaccines. This highlights the need to develop more effective vaccines for use during pregnancy and lactation to provide the breastfed infant with the best levels of protection.

In areas where COVID-19 vaccines are free for potential passive immunization of infants and young children through breastfeeding or milk sharing, these data suggest that the Moderna vaccine is ideal, while the J&J vaccine should be considered a last resort.

*Important warning

medRxiv publishes preliminary, non-peer-reviewed scientific reports and should therefore not be considered conclusive, guiding clinical practice/health-related behavior, or treated as established knowledge.

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