Antibody-mediated protection against MERS-CoV in the murine model.

Murine antisera with neutralising activity for the coronavirus causative of Middle East respiratory syndrome (MERS) were induced by immunisation of Balb/c mice with the receptor binding domain (RBD) of the viral Spike protein. The murine antisera induced were fully-neutralising in vitro for two separate clinical strains of the MERS coronavirus (MERS-CoV). To test the neutralising capacity of these antisera in vivo, susceptibility to MERS-CoV was induced in naive recipient Balb/c mice by the administration of an adenovirus vector expressing the human DPP4 receptor (Ad5-hDPP4) for MERS-CoV, prior to the passive transfer of the RBD-specific murine antisera to the transduced mice. Subsequent challenge of the recipient transduced mice by the intra-nasal route with a clinical isolate of the MERS-CoV resulted in a significantly reduced viral load in their lungs, compared with transduced mice receiving a negative control antibody. The murine antisera used were derived from mice which had been primed sub-cutaneously with a recombinant fusion of RBD with a human IgG Fc tag (RBD-Fc), adsorbed to calcium phosphate microcrystals and then boosted by the oral route with the same fusion protein in reverse micelles. The data gained indicate that this dual-route vaccination with novel formulations of the RBD-Fc, induced systemic and mucosal anti-viral immunity with demonstrated in vitro and in vivo neutralisation capacity for clinical strains of MERS-CoV.

Initial relapses in previously treated Hodgkin's disease. I. Results of second treatment.

Two hundred forty-three consecutive patients with Hodgkin's disease who relapsed after an initial course of treatment at the Stanford University Division of Radiation Therapy underwent subsequent systematic evaluation and retreatment. An analysis of the influence of numerous parameters, including sex, histopathology, original stage, relapse site, and original and second therapy, on actuarial survival and on relapse-free survival was undertaken. Most relapses (87%) occurred within 3 years of the initial treatment course. The 5-year relapse-free survival measured from the time of second treatment increased from 14% before to 39% after the introduction of multiple agent chemotherapy (MOPP) for relapsing disease. Patients treated with MOPP chemotherapy for nodal relapses showed increased subsequent relapse-free survival (61%) when compared with patients treated only with radiotherapy for nodal relapses. Based on the combined findings of this analysis, recommendations are made regarding the management of patients with Hodgkin's disease who have suffered a relapse.

Carcinoma of the oropharynx. Results of megavoltage radiation therapy in 305 patients.

Three hundred and five patients with oropharyngeal carcinomas received linear accelerator radiation therapy at the Stanford University Medical Center between 1956 and 1973. All were staged by the TNM system, using the UICC Classification of 1962. Actuarial five year survival for patients with tonsil cancers ranged from 50% to 18% for those with T1 and T3 lesions, respectively. Disease-free survival was higher than actuarial survival for patients with T1 and T2 lesions, reflecting an alteration of the latter curves by deaths from intercurrent diseases and second primary malignancies. Actuarial survival for patients with base of the tongue carcinomas was approximately 35% for those with T1 and T2 primary lesions and 22% for patients with T3 carcinomas. Considering all oropharyngeal sites of involvement together, clinically involved cervical lymph nodes were controlled by radiation therapy alone in 60 of 91 patients with N1 nodal involvement (67%), in twelve of 25 with N2 neck disease (48%) and in 46% of those patients with N3 involvement (34 of 74). Eighty-nine percent of patients whose lymph nodes were not controlled by radiation therapy alone also had uncontrolled primary cancers. Over 90% of the patients whole cervical lymph nodes were initially uninvolved remained free of late nodal metastases if at least the regional (first echelon) lymph nodes were included in the primary treatment fields. The results of a randomized trial which compared surgery and radiation therapy alone and the two modalities in combination for the treatment of a limited number of patients with advanced cancers of the oropharynx, supraglottic larynx and hypopharynx suggest that surgery alone is not the treatment of choice.

Irradiation of clinically uninvolved cervical lymph nodes.

Of 402 patients with cancers of the oral cavity, oropharynx, and supraglottic larynx treated at Stanford between 1957 and 1972, 164 had clinically uninvolved cervical lymph nodes prior to the initiation of radiation therapy. Lymph node metastases developed later in 38 per cent of patients with primary oral cavity carcinomas who were treated with interstitial radium implants alone. No late cervical lymph node involvement was found in those patients who received high dose external irradiation to at least the primary site and first echelon lymph nodes. Lymph node failures were ultimately noted in 20 of the 140 patients (14 per cent), who received partial or complete neck irradiation, but 18 of these occurred in patients with uncontrolled primary lesions, suggesting that re-seeding of cervical lymph nodes had taken place rather than failure of the initial irradiation to control subclinical metastases. Our present policy is to treat the primary lesion and adjacent lymph nodes with high dose megavoltage techniques, combined with interstitial irradiation if possible. Bilateral supplemental inferior neck radiation ports are added for patients with advanced primary neoplasms and for those with clinically involved cervical lymph nodes. All other patients undergoing radiation therapy for stage T1 primary lesions and clinically negative necks also receive ipsilateral low neck irradiation. In addition, cervical lymph nodes are electively irradiated when the primary lesion has been resected. When these policies are adopted, the incidence of cervical lymph node failures is extremely low in patients whose primary sites remain controlled, and morbidity from the cervical radiation fields is negligible.