It has been extremely difficult to elicit broadly cross-reactive neutralizing antibodies (Nabs) against human immunodeficiency virus type 1 (HIV-1). In this study, we compared the immunogenic properties of the wild-type and variable loop-deleted HIV-1 envelope glycoproteins. Mice were immunized with recombinant vaccinia viruses expressing either the wild-type or the variable loop-deleted (V1-2, V3, V4, and V1-3) HIV-1(DH12) gp160s. The animals were subsequently boosted with respective recombinant gp120s. All envelope constructs elicited similar levels of gp120-binding antibodies when analyzed by enzyme-linked immunosorbent assay (ELISA). However, the highest neutralizing activity was observed in sera from animals immunized with the wild-type envelope protein, followed by those immunized with DeltaV4 and DeltaV1-2. No neutralizing activity was detected in sera from animals immunized with DeltaV3 or DeltaV1-3. To identify immunogenic epitopes, ELISA was performed with overlapping 15-mer peptides that cover the entire length of gp120. For the wild-type gp120, the immunogenic epitopes mapped primarily to the variable loops V1-2 and to the conserved regions C1 and C5. When they were plotted onto known coordinates of gp120 core crystal structure, the epitopes in the conserved regions mapped predominantly to the inner domain of the protein. By immunizing with variable loop-deleted envelopes, the immune responses could be redirected to other regions of the protein. However, the newly targeted epitopes were neither on the exposed surface of the protein nor on the receptor binding regions. Interestingly, the removal of the V3 loop resulted in loss of immunoreactivity for both V3 and V1/V2 loops, suggesting structural interaction between the two regions. Our results suggest that obtaining broadly reactive Nabs may not be achieved simply by deleting the variable loops of gp120. However, the observation that the immune responses could be redirected by altering the protein composition might allow us to explore alternative strategies for modifying the antigenic properties of HIV-1 envelope glycoprotein.

BACKGROUND: Perinatal practices such as breast-feeding, kangaroo mother care, rooming-in, and delayed cord clamping have varied by institution during the COVID-19 pandemic. The goal of this systematic review was to examine the success of different practices in preventing viral transmission between SARS-CoV-2 positive mothers and their infants. METHODS: Electronic searches were performed in the Ovid MEDLINE, Ovid Embase, Cochrane Library, EBSCOhost CINAHL Plus, Web of Science, and Scopus databases. Studies involving pregnant or breastfeeding patients who tested positive for SARS-CoV-2 by RT-PCR were included. Infants tested within 48 hours of birth who had two tests before hospital discharge were included. Infants older than one week with a single test were also included. RESULTS: Twenty eight studies were included. In the aggregated data, among 190 breastfeeding infants, 22 tested positive for SARS-CoV-2 (11.5%), while 4 of 152 (2.63%) among bottle-fed (Fisher’s exact test p = 0.0006). The positivity rates for roomed in infants (20/103, 19.4%) were significantly higher than those isolated (5/300, 1.67%) (P <  0.0001). There was no significant difference in positivity rate among infants who received kangaroo care (25%vs 9%, p = 0.2170), or delayed cord clamping (3.62%vs 0.9%, p = 0.1116). CONCLUSIONS: Lack of robust studies involving large patient population does not allow meaningful conclusions from this systematic review. Aggregated data showed increased positivity rates of SARS-CoV-2 among infants who were breast fed and roomed-in. There were no differences in SARS-CoV-2 positivity rates in infants received skin to skin care or delayed cord clamping.