The SARS-CoV-2 immune response in human milk has not yet been examined, though protecting infants and young children from COVID-19 is critical for limiting community transmission, and preventing serious illness and death. Here, milk samples from 8 COVID-19-recovered and 7 COVID-19-suspected donors were tested for antibody (Ab) binding to the SARS-CoV-2 Spike protein. All samples exhibited significant specific IgA reactivity to the full Spike, while 80% exhibited significant IgA and secretory (s)Ab binding to the receptor binding domain (RBD). Additionally, 67% of samples exhibited IgG and/or IgM binding to RBD. IgA and sAb titers were highly correlated, indicating most IgA to be sIgA. Overall, these data indicate that a robust sIgA-dominant SARS-CoV-2 Ab response in human milk after infection should be expected in a significant majority of individuals. Further research is highly warranted to determine Ab functionality, and the potential for exploiting extracted milk sIgA for therapeutic use.

SARS-CoV-2, commonly termed COVID-19 for the illness it causes, has infected >3.2 million people, including >220,000 deaths. Human milk IgG originates mainly from blood, therefore a SARS-CoV-2-reactive antibody (Ab) response in milk would be expected (1). However, IgG comprises only ~2% of milk Ab, with most milk Abs originating from mucosa-associated

The global COVID-19 pandemic has put enormous stress on healthcare systems and hospital staffing. However, through all this, families will continue to become pregnant, give birth, and breastfeed. Unfortunately, care of the childbearing family has been de-prioritized during the pandemic. Additionally, many healthcare practices during the pandemic have not been positive for the childbearing family or breastfeeding. Despite recommendations from the World Health Organization to promote early, direct breastfeeding and skin to skin contact, these and other recommendations are not being followed in the clinical setting. For example, some mothers have been forced to go through labor and birth alone in some institutions whilst some hospitals have limited or no parental visitation to infants in the NICU. Furthermore, hospitals are discharging mothers and their newborns early, limiting the amount of time that families receive expert lactation care, education, and technical assistance. In addition, some hospitals have furloughed staff or transferred them to COVID-19 wards, further negatively impacting direct care for families and their newborns. We are concerned that these massive changes in the care of childbearing families will be permanently adopted. Instead, we must use the pandemic to underscore the importance of human milk and breastfeeding as lifesaving medical interventions. We challenge healthcare professionals to change the current prenatal and post-birth practice paradigms to protect lactation physiology and to ensure that all families in need receive equal access to evidence-based lactation education, care and technical assistance.

f ; Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts, USA g Broadly neutralizing antibodies (bNAbs) PG9 and PG16 were isolated from an International AIDS Vaccine Initiative (IAVI) Protocol G subject infected with human immunodeficiency virus type 1 (HIV-1) clade A. Both antibodies are highly potent and neutralize greater than 70% of viruses tested. We sought to begin immunogen design based on viral sequences from this patient; however, pseudoviruses prepared with 19 envelope sequences from this subject were resistant to neutralization by PG9 and PG16. Therefore, we used a bioinformatics approach to identify closely related viruses that were potentially sensitive to PG9 and PG16. A most-recent common ancestor (MRCA) sequence for the viral envelope (Env) was determined and aligned with 99 subtype A gp160 sequences from the Los Alamos HIV database. Virus BG505.W6M.ENV.C2 (BG505) was found to have the highest degree of homology (73%) to the MRCA sequence. Pseudoviruses prepared with this Env were sensitive to neutralization with a broad panel of bNAbs, including PG9 and PG16. When expressed by 293T cells as soluble gp120, the BG505 monomer bound well to both PG9 and PG16. We further showed that a point mutation (L111A) enabled more efficient production of a stable gp120 monomer that preserves the major neutralization epitopes. Finally, we showed that an adjuvanted formulation of this gp120 protein elicited neutralizing antibodies in rabbits (following a gp120 DNA vaccine prime) and that the antisera competed with bNAbs from 3 classes of nonoverlapping epitopes. Thus, the BG505 Env protein warrants further investigation as an HIV vaccine candidate, as a stand-alone protein, or as a component of a vaccine vector.

High-risk cohorts in East Africa and the United States show rates of dual HIV-1 infection-the concomitant or sequential infection by two HIV-1 strains-of 50% to 100% of those of primary infection, and our normalrisk HIV-positive cohort in Cameroon exhibits a rate of dual infection of 11% per year, signifying that these infections are not exceptional. Little is known regarding the effect of dual infections on host immunity, despite the fact that they provide unique opportunities to investigate how the immune response is affected when challenged with diverse HIV-1 antigens. Using heterologous primary isolates, we have shown here that dual HIV-1 infection by genetically distant strains correlates with significantly increased potency and breadth of the anti-HIV-1 neutralizing antibody response. When the neutralization capacities of sequential plasma obtained before and after the dual infection of 4 subjects were compared to those of matched plasma obtained from 23 singly infected control subjects, a significant increase in the neutralization capacity of the sequential sample was found for 16/28 dually infected plasma/virus pairs, while only 4/159 such combinations for the control subjects exhibited a significant increase (P < 0.0001). Similarly, there was a significant increase in the plasma dilution capable of neutralizing 50% of virus (IC 50 ) for 18/24 dually infected plasma/virus pairs, while 0/36 controls exhibited such an increase (P < 0.0001). These results demonstrate that dual HIV-1 infection broadens and strengthens the anti-HIV-1 immune response, suggesting that vaccination schemes that include polyvalent, genetically divergent immunogens may generate highly protective immunity against any HIV-1 challenge strain.