A ferritin-based COVID-19 nanoparticle vaccine that elicits robust, durable, broad-spectrum neutralizing antisera in non-human primates.

While the rapid development of COVID-19 vaccines has been a scientific triumph, the need remains for a globally available vaccine that provides longer-lasting immunity against present and future SARS-CoV-2 variants of concern (VOCs). Here, we describe DCFHP, a ferritin-based, protein-nanoparticle vaccine candidate that, when formulated with aluminum hydroxide as the sole adjuvant (DCFHP-alum), elicits potent and durable neutralizing antisera in non-human primates against known VOCs, including Omicron BQ.1, as well as against SARS-CoV-1. Following a booster ~one year after the initial immunization, DCFHP-alum elicits a robust anamnestic response. To enable global accessibility, we generated a cell line that can enable production of thousands of vaccine doses per liter of cell culture and show that DCFHP-alum maintains potency for at least 14 days at temperatures exceeding standard room temperature. DCFHP-alum has potential as a once-yearly (or less frequent) booster vaccine, and as a primary vaccine for pediatric use including in infants.

A ferritin-based COVID-19 nanoparticle vaccine that elicits robust, durable, broad-spectrum neutralizing antisera in non-human primates.

While the rapid development of COVID-19 vaccines has been a scientific triumph, the need remains for a globally available vaccine that provides longer-lasting immunity against present and future SARS-CoV-2 variants of concern (VOCs). Here, we describe DCFHP, a ferritin-based, protein-nanoparticle vaccine candidate that, when formulated with aluminum hydroxide as the sole adjuvant (DCFHP-alum), elicits potent and durable neutralizing antisera in non-human primates against known VOCs, including Omicron BQ.1, as well as against SARS-CoV-1. Following a booster ∻one year after the initial immunization, DCFHP-alum elicits a robust anamnestic response. To enable global accessibility, we generated a cell line that can enable production of thousands of vaccine doses per liter of cell culture and show that DCFHP-alum maintains potency for at least 14 days at temperatures exceeding standard room temperature. DCFHP-alum has potential as a once-yearly booster vaccine, and as a primary vaccine for pediatric use including in infants.

MGNREGA in the Times of COVID-19 and Beyond: Can India do More with Less?

Covid-19 has ushered in a renewed focus on health, sanitisation and, in unexpected ways, on the need for productive employment opportunities in rural India. MGNREGA, the rural employment guarantee programme, has had a mixed track record in terms of providing adequate employment to those who need it the most, the quality of asset creation and adequacy of wages offered. This paper makes a case for reorienting a small portion of MGNREGA spending to create micro-entrepreneurs out of the 'reverse migrating' masons, electricians, plumbers and others in rural areas who can directly contribute to augmenting health and sanitization infrastructure in the likely new normal. This will provide relief to those whose livelihoods have been severely impacted and eventually lower dependence on public finances. We propose approval of a new work type for sanitization works without any hard asset creation under MGNREGA and roping in the private sector for its project management skills to quickly skill up the returning migrants as well as to match work with workers on an ongoing basis.

Temperature dependent soret spectral band shifts accompany human CN-mesohemoglobin assembly.

The interaction between human apohemoglobin A and CN-Mesohemin, a monomeric non-native heme derivative, was probed by Soret spectrophotometric titrations in 0.05 M potassium phosphate buffer, pH 7 at varied temperatures. Hypsochromic shifts in the absorbance maxima were observed at all temperatures below 10 degrees C. First derivative spectroscopy of CN-Mesohemin titrations was used to provide further evidence of a spectral shift upon CN-Mesohemoglobin assembly. Findings of Soret Spectral shifts demonstrate a preference for the alpha chain heme site by CN-Mesohemin indicative of semi-alpha-hemoglobin intermediate formation. CN-Mesohemin, a derivative with peripheral 2,4 ethyl groups, does not possess the extended conjugation seen for native CN-Protohemin with its 2,4 vinyl groups. Indeed, reduced polarity of CN-Mesohemin over that of CN-Protohemin resulted in distinct temperature dependencies. Molecular visualization and protein-ligand interaction analysis targeted a functionally diverse residue unique to the alpha-chain. Tyrosine-42 (a polar/non-polar amino acid) appeared to play a prominent role in the assembly process.

Soret spectral and bioinformatic approaches provide evidence for a critical role of the alpha -subunit in assembly of tetrameric hemoglobin.

Soret spectral contributions of the alpha-subunit heme pocket have been evaluated by performing static titrations of apohemoglobin A with CNProtohemin under varied experimental conditions. Increasing the temperature from 5 to 30 degrees C in 0.05 M potassium phosphate buffer, pH 7, resulted in a decreasingly prominent hypsochromic shifts reflecting altered the vinyl-globin interactions. Studies at 10 degrees C in over pH range of 6.7-8.0 revealed a profile for the spectral shifts approximating the side chain pK value (7.4) a histidyl residue. These overall spectral changes correspond to DeltaE of < or = 7 kJ/mol indicative of electrostatic noncovalent interactions. Further our current molecular modeling studies indicate that the spatial arrangement and critical noncovalent interactions of tyrosine 42 and histidine 45 (aromatic residues unique to the alpha-subunit) make significant contribution to the Soret spectra. Most interestingly, phylogenetic analyses have revealed the presence of a histidyl triad in the alpha-chain of all vertebrates that form heterotetramers.

Ordered heme binding ensures the assembly of fully functional hemoglobin: a hypothesis.

The exact mechanism by which four Fe-Protoporphyrin-IX (heme) moieties and four nascent globin chains combine to form human hemoglobin (alpha(2)beta(2)) remains a mystery. Recent Soret spectral static and kinetic studies of the incorporation of CN-Hemin derivatives into an array of human globin species have provided in vitro evidence of an ordered assembly pathway, through an alphaheme-betaglobin intermediate, that ensures correct formation of active hemoglobin tetramers.